Environmental exposure to cadmium and risk of cancer: a prospective population-based study (original) (raw)

Risk of mortality, cancer incidence, and stroke in a population potentially exposed to cadmium

Occupational and Environmental Medicine, 2000

Objectives-To follow up mortality and cancer incidence in a cohort potentially exposed to cadmium and to perform a geographical (ecological) analysis to further assess the health eVects of potential exposure to cadmium. Methods-The English village of Shipham has very high concentrations of cadmium in the soil. A previous cohort study of residents of Shipham in 1939 showed overall mortality below that expected, but a 40% excess of mortality from stroke. This study extends the follow up of the cohort for mortality to 1997, and includes an analysis of cancer incidence from 1971 to 1992, and a geographical study of mortality and cancer incidence. Standardised mortality and incidence ratios (SMRs and SIRs) were estimated with regional reference rates. Comparisons were made with the nearby village of Hutton. Results-All cause cohort mortality was lower than expected in both villages, although there was excess cancer incidence in both Shipham (SIR 167, 95% confidence interval (95% CI) 106 to 250) and Hutton (SIR 167, 95% CI 105 to 253). There was an excess of mortality from hypertension, cerebrovascular disease, and nephritis and nephrosis, of borderline significance, in Shipham (SMR 128, 95% CI 99 to 162). In the geographical study, all cause mortality in Shipham was also lower than expected (SMR 84, 95% CI 71 to 100). There was an excess in genitourinary cancers in both Shipham (SIR 160, 95% CI 107 to 239) and Hutton (SIR 153, 95% CI 122 to 192). Conclusion-No clear evidence of health eVects from possible exposure to cadmium in Shipham was found despite the extremely high concentrations of cadmium in the soil. (Occup Environ Med 2000;57:94-97)

Determinants of lung cancer risk among cadmium-exposed workers

Annals of Epidemiology, 1992

Workers at a cadmium recovery pIant in Globe, Colorado, showed an increased risk of lung cancer, which some investigators have attributed to cadmium exposure. We conducted a cohort mortality analysis of this work force and a case-control analysis of the lung cancer cases within this work force in order to assess the probable causes of the lung cancer excess. The Globe plant began as a lead smelter about 1886, switched to arsenic production in 1920, and became a cadmium metal production facility in 1926. Cadmium, arsenic, and cigarette smoking are three potential lung carcinogens found in this workplace. Industrial hygiene data collected from I943 onward served as the basis for the National Institute for Occupational Safety and Health (NIOSH)-derived exposure algorithm that assigned cadmium exposure estimates to employees based on their work area in the plant and calendar time. Few exposure data existed for substunces other than cadmium. Feedstock ore concentrations were used us a surrogate measure of air arsenic levels. The arsenic content of the fines used as feedstock prior to I940 was considerably higher than rhat of the fines used after 1940. Smoking histories had been obtained previously for 45% of the workers. A case-control analysis of the 25 cases of lung cancer known to have occurred among these workers through 1982 was conducted using three controls per case, matched by closest data of hire and age at hire. Porenrial causal agents for lung cancer included cadmium exposure, cigarette smoking, and arsenic exposure. Exposure variables for each case and control included estimated cumulative cadmium exposure in milligram-years per cubic meter, cigarette smoking history, and plant arsenic exposure status at the time of hire. Estimated cumuhtiwe cadmium exposures of cases and controls did not differ overall or within the date-of-hire strata. Cases were more than eight rimes more likely to have been cigarette smokers than were controls. Lung cancer risk in this workplace was more closely related to the period of hire, not to the cumulative cadmium eqosure. The period of hire appears to be a surrogate for arsenic exposure as related to feedstock. The measures used here seem to indicate that exposure to arsenic and cigarette particulates, rather than to cadmium particulates, may have caused the increased rate of lung cancer of these workers. Ann Epidemiol I992;2; 195-2 11.

Cadmium-Related Mortality and Long-Term Secular Trends in the Cadmium Body Burden of an Environmentally Exposed Population

Environmental Health Perspectives, 2008

BACKGROUND: Few population studies have reported on the long-term changes in the internal cadmium dose and simultaneously occurring mortality. OBJECTIVE: We monitored blood cadmium (BCd), 24-hr urinary cadmium (UCd), and mortality in an environmentally exposed population. METHODS: Starting from 1985, we followed BCd (until 2003), UCd (until 1996), and mortality (until 2007) among 476 and 480 subjects, randomly recruited from low-exposure areas (LEA) and high-exposure areas (HEA). The last cadmium-producing plant in the HEA closed in 2002. RESULTS: From 1985-1989 to 1991-1996, BCd decreased by 40.3% and 18.9% in the LEA and HEA, respectively (p < 0.0001 for between-area difference). From 1991-1996 until 2001-2003, BCd remained unchanged in the HEA (+ 1.8%) and increased by 19.7% in the LEA (p < 0.0001). Over the entire follow-up period, the annual decrease in BCd averaged 2.7% in the LEA (n = 258) and 1.8% in the HEA (n = 203). From 1985-1989 to 1991-1996, UCd fell by 12.9% in the LEA and by 16.6% in the HEA (p = 0.22), with mean annual decreases of 2.7% (n = 366) and 3.4% (n = 364). Over 20.3 years (median), 206 deaths (21.5%) occurred. At baseline, BCd (14.6 vs. 10.2 nmol/L) and UCd (14. nmol/24-hr) were higher in deaths than in survivors. The risks (p ≤ 0.04) associated with a doubling of baseline UCd were 20% and 44% for total and noncardiovascular mortality, and 25% and 33% for a doubling of BCd. CONCLUSIONS: Even if zinc-cadmium smelters close, historical environmental contamination remains a persistent source of exposure. Environmental exposure to cadmium increases total and noncardiovascular mortality in a continuous fashion without threshold.

Cancer mortality of cadmium workers

Occupational and Environmental Medicine, 1985

Several epidemiological studies of workers exposed to cadmium indicate an increased risk of lung and prostatic cancer. The increase is statistically significant in some of the studies but the SMR is greater than 100 in almost all. A cohort study of the mortality among 522 Swedish workers exposed to cadmium for at least one year in a nickel-cadmium battery plant support the earlier findings. The SMR for lung and prostatic cancer increased with increasing dose and latency but did not obtain statistical significance. A combination of all the available data from the most recent follow up of causes of death among cadmium workers in six different cohorts shows 28 cases of prostatic cancer (SMR = 162) and 195 cases of lung cancer (SMR = 121). This new analysis suggests that long term, high level exposure to cadmium is associated with an increased risk of cancer. The role of concomitant exposure to nickel needs further study.

Determinants of Cadmium Burden Levels in a Population of Children Living in the Vicinity of Nonferrous Smelters

Environmental Research, 2001

This report covers part of the assessment of a site in northern France polluted by industrial metal emissions. Our objectives were to assess the cadmium burden in children aged 8 to 11 years and look for factors that affected it. A cross-sectional population-based study took place in 1996+1997 and included 400 children (200 in the metal-polluted area). The geometric mean of the blood cadmium (CdB) levels of children living on the polluted site was 0.51 g/L (95% CI ‫؍‬ [0.49+0.53]); that of the nonexposed children was 0.47 g/L (95% CI ‫؍‬ [0.45+0.49]) (P < 0.01). The geometric mean of the urinary cadmium (CdU) levels of children living on the polluted site was 1.16 g/g creatinine (95% CI ‫؍‬ [1.01+1.34]); that of the nonexposed children was 0.99 g/g creatinine (95% CI ‫؍‬ [0.86+1.14]) (P ‫؍‬ 0.10). Mean CdB was higher among children within 4 km of a zinc smelter and consuming 5500 ml of tap water daily ( ؋ 1.34; 95% CI ‫؍‬ [1.14+1.51]) compared with children living more than 4 km away and consuming < 500 ml of tap water daily. Independently of this association, consumption of Ash and shellAsh (5once a week vs < once a week) and homegrown vegetables (5once daily vs < once daily) was associated with higher mean CdB levels, respectively: ؋ 1.14; 95% CI ‫؍‬ [1.07+1.21] and ؋ 1.25; 95% CI ‫؍‬ [1.04+1.50]. Neither sex nor age was associated with CdB. Mean CdU was associated with paternal occupational cadmium exposure.

Cadmium Exposure and Breast Cancer Risk

JNCI Journal of the National Cancer Institute, 2006

Cadmium, a highly persistent heavy metal, has been categorized as a probable human carcinogen by the U.S. Environmental Protection Agency. Primary exposure sources include food and tobacco smoke. We carried out a population-based case -control study of 246 women, aged 20 -69 years, with breast cancer and 254 agematched con trol subjects. We measured cadmium levels in urine samples by inductively coupled plasma mass spectrometry and conducted interviews by telephone to obtain information on known breast cancer risk factors. Odds ratios (ORs) and 95% confi dence intervals (CIs) for breast cancer by creatinine-adjusted cadmium levels were calculated by multivariable analysis. Statistical tests were two-sided. Women in the highest quartile of creatinine-adjusted cadmium level ( ≥ 0.58 µg/g) had twice the breast cancer risk of those in the lowest quartile (<0.26 µg/g; OR = 2.29, 95% CI = 1.3 to 4.2) after adjustment for established risk factors, and there was a statistically signifi cant increase in risk with increasing cadmium level ( P trend = .01). Based on this study, the absolute risk difference is 45 (95% CI = 0 to 77) per 100 000 given an overall breast cancer rate of 124 per 100 000. Whether increased cadmium is a causal factor for breast cancer or refl ects the effects of treatment or disease remains to be determined. [J Natl Cancer Inst 2006;98: 869 -73 ]

Biological Effects of Human Exposure to Environmental Cadmium

Biomolecules

Cadmium (Cd) is a toxic metal for the human organism and for all ecosystems. Cd is naturally found at low levels; however, higher amounts of Cd in the environment result from human activities as it spreads into the air and water in the form of micropollutants as a consequence of industrial processes, pollution, waste incineration, and electronic waste recycling. The human body has a limited ability to respond to Cd exposure since the metal does not undergo metabolic degradation into less toxic species and is only poorly excreted. The extremely long biological half-life of Cd essentially makes it a cumulative toxin; chronic exposure causes harmful effects from the metal stored in the organs. The present paper considers exposure and potential health concerns due to environmental cadmium. Exposure to Cd compounds is primarily associated with an elevated risk of lung, kidney, prostate, and pancreatic cancer. Cd has also been linked to cancers of the breast, urinary system, and bladder. ...

Cadmium-induced cancers in animals and in humans

International journal of occupational and environmental health

Discovered in the early 1800s, the use of cadmium and various cadmium salts started to become industrially important near the close of the 19th century, rapidly thereafter began to flourish, yet has diminished more recently. Most cadmium used in the United States is a byproduct from the smelting of zinc, lead, or copper ores, and is used to manufacture batteries. Carcinogenic activity of cadmium was discovered first in animals and only subsequently in humans. Cadmium and cadmium compounds have been classified as known human carcinogens by the International Agency for Research on Cancer and the National Toxicology Program based on epidemiologic studies showing a causal association with lung cancer, and possibly prostate cancer, and studies in experimental animals, demonstrating that cadmium causes tumors at multiple tissue sites, by various routes of exposure, and in several species and strains. Epidemiologic studies published since these evaluations suggest that cadmium is also asso...

Cadmium Toxicity in Nature Generates the Cancerous Problems

Pollution Research

A naturally occurring metal, cadmium is noticed in tiny amounts in a variety of sources such as food, water, soil, and the atmosphere. Cadmium may be edified in all soils and rocks, including coal and mineral fertilizers. In general, non-smoker people are getting affected by food contamination. The main theme of this paper is cancer activity by cadmium pollution of our environment. Foods are getting contaminated by industrial wastes. Wastes have Cd2+ ions which can bind with plant materials and also bind with animal muscles. On the other hand, the smoker people take the cadmium by smoking tobacco. The cadmium can easily bind up with the organs like the lung, prostate, breast, bone, etc. When industrial wastes are thrown into rivers, ponds, or open spaces, particularly in South Asian nations, the water becomes poisoned and the soil becomes deteriorated; as a result, the environment becomes more hazardous. In consequence, people can be oppressed by significant sicknesses that occurred...

Cadmium exposure in the population: from health risks to strategies of prevention

BioMetals, 2010

We focus on the recent evidence that elucidates our understanding about the effects of cadmium (Cd) on human health and their prevention. Recently, there has been substantial progress in the exploration of the shape of the Cd concentrationresponse function on osteoporosis and mortality. Environmental exposure to Cd increases total mortality in a continuous fashion without evidence of a threshold, independently of kidney function and other classical factors associated with mortality including age, gender, smoking and social economic status. Pooled hazard rates of two recent environmental population based cohort studies revealed that for each doubling of urinary Cd concentration, the relative risk for mortality increases with 17% (95% CI 4.2-33.1%; P \ 0.0001). Tubular kidney damage starts at urinary Cd concentrations ranging between 0.5 and 2 lg urinary Cd/g creatinine, and recent studies focusing on bone effects show increased risk of osteoporosis even at urinary Cd below 1 lg Cd/g creatinine. The non-smoking adult population has urinary Cd concentrations close to or higher than 0.5 lg Cd/g creatinine. To diminish the transfer of Cd from soil to plants for human consumption, the bioavailability of soil Cd for the plants should be reduced (external bioavailability) by maintaining agricultural and garden soils pH close to neutral (pH-H 2 O of 7.5; pH-KCL of 6.5). Reducing the systemic bioavailability of intestinal Cd can be best achieved by preserving a balanced iron status. The latter might especially be relevant in groups with a lower intake of iron, such as vegetarians, and women in reproductive phase of life. In exposed populations, house dust loaded with Cd is an additional relevant exposure route. In view of the insidious etiology of health effects associated with low dose exposure to Cd and the current European Cd intake which is close to the tolerable weekly intake, one should not underestimate the importance of the recent epidemiological evidence on Cd toxicity as to its medical and public health implications.

Breast cancer frequency and exposure to cadmium: A meta-analysis and systematic review

2013

Background: In this meta-analysis we review evidence suggesting that exposure to cadmium is a cause of breast cancer. Materials and Methods: We conducted Medline/PubMed and Scopus searches using selected MeSH keywords to identify papers published from January 1, 1980 through January 1, 2013. Data were merged and summary mean differences were estimated using either a random-effects model or a fixed-effects model. Results: There were 13 studies including 978 exposed cases and 1,279 controls. There was no statistically significant difference in the frequencies of breast cancer between cadmium-exposed and control groups, and the summary estimate of mean difference was 0.71 (95%CI: 0.33-1.08). However, stratification showed that there were statistically significant differences in the frequencies of breast cancer between cadmium-exposed and control groups among Asian compared with Caucasian population, and the summary estimates of mean difference were 1.45 (95%CI: 0.62-2.28) vs. 0.25 (95%CI: -0.09-0.6), respectively. There was a difference in the frequencies of breast cancer between cadmium-exposed and control groups in peripheral venous blood sampling methods, and the summary estimate of mean difference was 1.41 (95%CI: 0.46-2.37). Conclusions: Data indicate that the frequencies of breast cancer might be an indicator of early genetic effects for cadmium-exposed populations. However, our meta-analysis was performed on population-based studies; meta-analysis based on individual data might provide more precise and reliable results. Therefore, it is necessary to construct an international database on genetic damage among populations exposed to cadmium that may contain all raw data of studies examining genetic toxicity.

Cadmium, Environmental Exposure, and Health Outcomes

Environmental Health Perspectives, 2009

Objectives: We provide an update of the issues surrounding health risk assessment of exposure to cadmium in food. Data sOurces: We reviewed epidemiologic studies published between 2004 and 2009 concerning the bioavailability of cadmium in food, assessment of exposure, and body burden estimate, along with exposure-related effects in nonoccupationally exposed populations. Data extractiOn anD synthesis: Bioavailability of ingested cadmium has been confirmed in studies of persons with elevated dietary exposure, and the findings have been strengthened by the substantial amounts of cadmium accumulated in kidneys, eyes, and other tissues and organs of environmentally exposed individuals. We hypothesized that such accumulation results from the efficient absorption and systemic transport of cadmium, employing multiple transporters that are used for the body's acquisition of calcium, iron, zinc, and manganese. Adverse effects of cadmium on kidney and bone have been observed in environmentally exposed populations at frequencies higher than those predicted from models of exposure. Increasing evidence implicates cadmium in the risk of diseases that involve other tissues and organ systems at cadmium concentrations that do not produce effects on bone or renal function. cOnclusiOns: Population data raise concerns about the validity of the current safe intake level that uses the kidney as the sole target in assessing the health risk from ingested cadmium. The data also question the validity of incorporating the default 5% absorption rate in the threshold-type risk assessment model, known as the provisional tolerable weekly intake (PTWI), to derive a safe intake level for cadmium.

Cadmium exposure and risk of prostate cancer: a meta-analysis of cohort and case-control studies among the general and occupational populations

Scientific Reports, 2016

We aimed to evaluate the association of cadmium exposure with the risk of prostate cancer in both the general and occupational populations. Online database searches were performed for studies of prostate cancer risk and cadmium exposure. Twelve cohort studies (5 in the general, 7 in occupational populations) and 9 case-control studies (3 in the general, 6 in occupational populations) were identified. Five/seven cohort studies in the general and occupational populations consist of 78,263/13, 434 participants with a mean follow-up of 12.1/43.0 years, respectively. Case-control studies include 334 cases/670 controls in the general population, and 1,315 cases/4,477 controls in occupational populations. Comparing the highest to the lowest category of cadmium exposure in the general population, the weighted relative risk of prostate cancer incidence and mortality among cohort studies, and the weighted odds ratio in case-control studies were 1.05 (95%CI [0.91, 1.22]), 0.83 (95%CI [0.35, 1.98]), and 1.27 (95%CI [0.58,2.78]), respectively. For occupational populations, the weighted OR in case-control studies was 1.17 (95%CI [0.85, 1.62]), and the weighted standardized mortality ratio in cohort studies was 98 (95%CI [75, 126]). Accumulated epidemiological evidence does not support the hypothesis that cadmium exposure may increase the risk of prostate cancer in either the general or occupational populations.

Risk assessment of effects of cadmium on human health (IUPAC Technical Report)

Pure and Applied Chemistry, 2018

Chemistry and Human Health, Division VII of the International Union on Pure and Applied Chemistry (IUPAC), provides guidance on risk assessment methodology and, as appropriate, assessment of risks to human health from chemicals of exceptional toxicity. The aim of this document is to describe dose-response relationships for the health effects of low-level exposure to cadmium, in particular, with an emphasis on causation. The term "cadmium" in this document includes all chemical species of cadmium, as well as those in cadmium compounds. Diet is the main source of cadmium exposure in the general population. Smokers and workers in cadmium industries have additional exposure. Adverse effects have been shown in populations with high industrial or environmental exposures. Epidemiological studies in general populations have also reported statistically significant associations with a number of adverse health effects at low exposures. Cadmium is recognized as a human carcinogen, a classification mainly based on occupational studies of lung cancer. Other cancers have been reported, but dose-response relationships cannot be defined. Cardiovascular disease has been associated with cadmium exposure in recent epidemiological studies, but more evidence is needed in order to establish causality. Adequate evidence of dose-response relationships is available for kidney effects. There is a relationship between cadmium exposure and kidney effects in terms of low molecular mass (LMM) proteinuria. Long-term cadmium exposures with urine cadmium of 2 nmol mmol −1 creatinine cause such effects in a susceptible part of the population. Higher exposures result in increases in the size of these effects. This assessment is supported by toxicokinetic and toxicodynamic (TKTD) modelling. Associations between urine cadmium lower than 2 nmol mmol −1 creatinine and LMM proteinuria are influenced by confounding by co-excretion of cadmium with protein. A number of epidemiological studies, including some on low exposures, have reported statistically significant associations between cadmium exposure and bone demineralization and fracture risk. Exposures leading to urine cadmium of 5 nmol mmol −1 creatinine and more increase the risk of bone effects. Similar associations at much lower urine cadmium levels have been reported. However, complexities in the cause and effect relationship mean that a no-effect level cannot be Article note: Sponsoring body: Chemistry and Human Health Division: see more details on p. xxx. a IUPAC Task Group on Risk assessment of Effects of Cadmium on Human Health.

Mortality of inhabitants in an area polluted by cadmium: 15 year follow up

Occupational and Environmental Medicine, 1995

Objective-To assess the influence of environmental exposure to cadmium (Cd) on long term outcome of inhabitants living in an area polluted by Cd. Methods-A follow up study for 15 years (from 1974-5 to 1991) was carried out on 2408 inhabitants (amounting to 95% of the target population, 1079 men and 1329 women) of the Kakehashi River basin in Ishikawa Prefecture, Japan. These inhabitants had been the subjects of the health impact survey in 1974-5 to evaluate (by measurement of urinary retinol binding protein (RBP)) renal dysfunction induced by Cd. Analysis of mortality was performed by dividing subjects into a urinary RBP positive ( > 4 mg/1) group and RBP negative (<4 mg/l) group. Results-After adjustment for age with Cox's proportional hazard model, RBP > 4 mg/l showed a significant relation to mortality in both sexes. At this time, the mortality risk ratio of the RBP positive to negative group was 1-71 in the men and 1*42 in the women. When the SMRs according to causes of deaths in the RBP positive group were compared with those of the RBP negative group or the overall Japanese population increases of SMR for cardiovascular diseases, especially heart failure, and renal diseases were found in both sexes. Conclusion-These results suggest that the prognosis of the exposed inhabitants with renal tubular dysfunction is unfavourable, and these increases of mortality are due to heart failure and renal diseases. (Occup Environ Med 1995;52:181-184) Keywords: environmental cadmium; retinol binding protein; mortality 65 (6-0) 1329 113 (8 5)

Cadmium, Environmental Exposure, and Health

2010

Objectives: We provide an update of the issues surrounding health risk assessment of exposure to cadmium in food. Data sources: We reviewed epidemiologic studies published between 2004 and 2009 concerning the bioavailability of cadmium in food, assessment of exposure, and body burden estimate, along with exposure-related effects in nonoccupationally exposed populations. Data extraction and synthesis: Bioavailability of ingested cadmium has been confirmed in studies of persons with elevated dietary exposure, and the findings have been strengthened by the substantial amounts of cadmium accumulated in kidneys, eyes, and other tissues and organs of environmentally exposed individuals. We hypothesized that such accumulation results from the efficient absorption and systemic transport of cadmium, employing multiple transporters that are used for the body's acquisition of calcium, iron, zinc, and manganese. Adverse effects of cadmium on kidney and bone have been observed in environmentally exposed populations at frequencies higher than those predicted from models of exposure. Increasing evidence implicates cadmium in the risk of diseases that involve other tissues and organ systems at cadmium concentrations that do not produce effects on bone or renal function. Conclusions: Population data raise concerns about the validity of the current safe intake level that uses the kidney as the sole target in assessing the health risk from ingested cadmium. The data also question the validity of incorporating the default 5% absorption rate in the threshold-type risk assessment model, known as the provisional tolerable weekly intake (PTWI), to derive a safe intake level for cadmium.

A global perspective on cadmium pollution and toxicity in non-occupationally exposed population

Toxicology Letters, 2003

Cadmium is a non-essential element that has high rates of soil to plant transference compared with other nonessential elements, and certain plant species accumulate large amounts of cadmium from low cadmium content soils. In this paper, levels of cadmium found in major food groups are highlighted together with cadmium levels found in liver and kidney samples from non-occupationally exposed populations. Data on human kidney cadmium levels identified recently, including the study in our own laboratory, are compared with older studies. Human-tissue cadmium contents showed large variations among individuals, but sources of the variation remain unknown. Exposure levels of 30 Á/50 mg per day have been estimated for adults and these levels have been linked to increased risk of bone fracture, cancer, kidney dysfunction and hypertension. Increased mortality was found among individuals showing signs of cadmium renal toxicity compared with those without such signs, suggesting that renal toxicity may be an early warning of complications, sub-clinical or clinical morbidity. #

Lung cancer risk associated with occupational exposure to nickel, chromium VI, and cadmium in two population-based case-control studies in Montreal

American Journal of Industrial Medicine, 2010

Background Nickel, chromium VI, and cadmium have been identified as lung carcinogens in highly exposed cohorts. The purpose of this study was to examine the etiological link between lung cancer and these metals in occupations, that usually entail lower levels of exposure than those seen in historical cohorts. Methods Two population-based case-control studies were conducted in Montreal, from 1979 to 1986 and from 1996 to 2001, comprising 1,598 cases and 1,965 controls. A detailed job history was obtained to evaluate lifetime occupational exposure to many agents, including nickel, chromium VI, and cadmium compounds. Results Lung cancer odds ratios were increased only among former or non-smokers: 2.5 (95% CI: 1.3-4.7) for nickel exposure, 2.4 (95% CI: 1.2-4.8) for chromium VI, and 4.7 (95% CI: 1.5-14.3) for cadmium. The metals did not increase risk among smokers. Conclusions While excess risks due to these metal compounds were barely discernable among smokers, carcinogenic effects were seen among non-smokers. Am. J. Ind. Med. 53:476-485,

Environmental Toxicity of Cadmium and Health Effect

Journal of environmental protection and ecology

environmental toxicology examines the fate and effects of contaminants in the environment. exposures to heavy metals can affect human health both directly or indirectly by disrupting ecological systems that exist in rivers, lake, oceans, streams, wetlands, estuaries and other ecosystems. It is known that cadmium input to the aquatic environment through discharge of industrial waste, surface run off and deposition of cadmium also strongly absorbed onto sediments and soils. on the other hand, non-ferrous metal mines and human activities such as using phosphate fertilisers, burning coal, iron alloys, steel and cement and disposing household waste, represent a major source of cadmium release to the aquatic ecosystems. cadmium can easily entered into the body by food chain, drinking water, smoking a cigarette or even breathing the air. acute and chronic exposure to cadmium in both human and animals results in health diseases. Cadmium was classified as a potential human carcinogen under t...

The effects of changes in cadmium and lead air pollution on cancer incidence in children

Science of The Total Environment, 2010

This article presents the results of research on the effects of air pollution on cancer incidence in children in the region of Silesia (Poland), which has undergone one of the most profound anthropogenic transformations in Europe. The main objective of the research was to specify the impact of changes in cadmium and lead pollution in the years 1990-2005 on the incidence of cancers reported in children. Lead concentration ranged from 0 to 1490 · 10 -9 G m −2 /year, and cadmium concentration ranged from 0 to 33.7 · 10 -9 G m −2 /year. There was no strong significant correlation (max 0.3) between air pollution and incidence rate (IR) in the general population of children in any particular year. Alongside the cartographic presentation of dependences, correlation coefficients between the variables in question were calculated. This made it possible to determine the relationship between the pollution levels and incidence rates in the area. There was a significant reduction in the level of pollution during the investigated period. The study of the relationship between the number of cancers reported and the condition of the natural environment revealed increased sensitivity to toxins in boys (correlation coefficient 0.3). In addition, the spatial distribution of the number of cases reported in boys suggests a correlation with the spatial distribution of the coefficients for the entire group of children included in the study. The yearly average IR of childhood cancer in specific districts ranged from 0 to 61.48/100,000 children under 18 years of age during the 1995-2004 period.

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Induction of metal binding compounds and antioxidative defence in callus cultures of two black poplar (P. nigra) clones with different tolerance to cadmium

Plant Cell, Tissue and Organ Culture (PCTOC), 2012

Callus cultures of two parental clones of Populus nigra L., Poli and 58-861, originating from contrasting environments, were exposed to different cadmium concentrations (0, 150 and 250 lM CdSO 4 ). Clones showed different growth responses to cadmium, evaluated by the tolerance index (Ti), with Poli being more tolerant to the metal at both concentrations. The cadmium concentration at the end of the treatment was very similar between clones at 150 lM CdSO 4 , while a higher value in 58-861 compared to Poli was detected at 250 lM CdSO 4 . The bioconcentration factor evidenced the lowest value in Poli at 250 lM CdSO 4 . Unlike 58-861, cadmium provoked a strong induction of thiols and phytochelatins in clone Poli. In both clones, organic acid concentration differed notably in untreated calli and cadmium treatment induced a general lowering of these compounds. A notably higher antioxidant enzyme activity (ascorbate peroxidase, APX; catalase, CAT; guaiacol peroxidase, GPX) was measured in control calli of clone Poli compared to 58-861. Cadmium induced a remarkable enhancement of APX and CAT, but not GPX, activity at 150 lM CdSO 4 in Poli. Conversely, in 58-861 at 150 lM CdSO 4 , and in both clones at 250 lM CdSO 4 , a decrease in the antioxidant activity occurred. This investigation provided evidence that these two contrasting genotypes of P. nigra are characterised by a different response to cadmium in callus cultures. In particular, in Poli, the higher tolerance to cadmium is associated with a higher activity of antioxidative enzymes and the ability to strongly increase thiol and PC concentration in response to metal exposure.

Zn2+/Cd2+ optical discrimination by fluorescent chemosensors based on 8-hydroxyquinoline derivatives and sulfur-containing macrocyclic units

Dalton Transactions, 2013

Four new fluorescent chemosensors for metal ions based on 8-hydroxyquinoline (8-HDQ) derivatives and sulfur-containing macrocyclic units were synthesized and characterized, namely 1-(5-chloro-8-hydroxy-7quinolinylmethyl)-1-aza-4,7,10-trithiacyclododecane (L1), 1-(5-chloro-8-hydroxy-7-quinolinylmethyl)-1aza-4,13-dithia-7,10-dioxacyclopentadecane (L2), 1-(8-hydroxy-2-quinolinylmethyl)-1-aza-4,7,10-trithiacyclododecane (L3), and 1-(8-hydroxy-2-quinolinylmethyl)-1-aza-4,13-dithia-7,10-dioxacyclopentadecane (L4). Preliminary fluorimetric titrations indicated L1 as the only member of the family of ligands to give a selective CHEF-type response to the presence of Zn 2+ in MeCN-H 2 O (1 : 1, v/v) solutions, which allowed imaging of this metal ion in Cos-7 cells in vitro. The other ligands either did not show any fluorescence response (L3, L4) to any of the metal ions considered (Cu 2+ , Zn 2+ , Cd 2+ , Hg 2+ and Pb 2+ ) or gave (L2) a CHEF-type response also to the presence of Cd 2+ . The coordination properties of L1 towards Zn 2+ were, therefore, fully investigated by potentiometric measurements and absorption and emission spectroscopy at different pH values, which indicated that the formation of 2 : 1 L1/Zn 2+ complexes is responsible for the CHEF-type effect observed. The complexes [Zn(L1) 2 H 2 O](BF 4 ) 2 and [Zn(L3)](ClO 4 ) 2 were characterized in the solid state by X-ray crystallography, and DFT calculations were performed to understand the origin of the Zn 2+ /Cd 2+ optical discrimination of the 8-HDQ-based "conjugate" fluorescent chemosensors reported. † Electronic supplementary information (ESI) available: Additional information as noted in the text including synthetic details for the preparation of L2-L4. CCDC 924214 for [Zn(L3)](ClO 4 ) 2 and 924216 for [Zn(L1) 2 H 2 O](BF 4 ) 2 . For ESI and crystallographic data in CIF or other electronic format see

Safety of food crops on land contaminated with trace elements

Journal of the Science of Food and Agriculture, 2011

Contamination of agricultural soils with trace elements (TEs) through municipal and industrial wastes, atmospheric deposition and fertilisers is a matter of great global concern. Since TE accumulation in edible plant parts depends on soil characteristics, plant genotype and agricultural practices, those soil-and plant-specific options that restrict the entry of harmful TEs into the food chain to protect human and animal health are reviewed. Soil options such as in situ stabilisation of TEs in soils, changes in physicochemical parameters, fertiliser management, element interactions and agronomic practices reduce TE uptake by food crops. Furthermore, phytoremediation and solubilisation as alternative techniques to reduce TE concentrations in soils are also discussed. Among plant options, selection of species and cultivars, metabolic processes and microbial transformations in the rhizosphere can potentially affect TE uptake and distribution in plants. For this purpose, genetic variations are exploited to select cultivars with low uptake potential, especially low-cadmium accumulator wheat and rice cultivars. The microbial reduction of elements and transformations in the rhizosphere are other key players in the cycling of TEs that may offer the basis for a wide range of innovative biotechnological processes. It is thus concluded that appropriate combination of soil-and plant-specific options can minimise TE transfer to the food chain.

Functional ecological genomics to demonstrate general and specific responses to abiotic stress

Functional Ecology, 2007

1. Stress is a major component of natural selection in soil ecosystems. The most prominent abiotic stress factors in the field are temperature extremes (heat, cold), dehydration (drought), high salinity and specific toxic compounds such as heavy metals. Organisms are able to deal with these stresses to a certain extent, which determines the limits of their ecological amplitudes. Functional genomic tools are now becoming available to study stress in ecologically relevant soil organisms.

Ectomycorrhizas with Paxillus involutus enhance cadmium uptake and tolerance in Populus × canescens

Plant, Cell & Environment, 2014

Ectomycorrhizas (EMs), which are symbiotic organs formed between tree roots and certain fungi, can mediate cadmium (Cd) tolerance of host plants, but the underlying physiological and molecular mechanisms are not fully understood. To investigate EMs mediated Cd tolerance in woody plants, Populus × canescens was inoculated with Paxillus involutus (strain MAJ) to establish mycorrhizal roots. Mycorrhizal poplars and non-mycorrhizal controls were exposed to 0 or 50 μM CdSO4. EMs displayed higher net Cd 2+ influx than non-mycorrhizal roots. Net Cd 2+ influx was coupled with net H + efflux and inactivation of plasma membrane (PM) H + -ATPases reduced Cd 2+ uptake of EMs less than of nonmycorrhizal roots. Consistent with higher Cd 2+ uptake in EMs, in most cases, transcript levels of genes involved in Cd 2+ uptake, transport and detoxification processes were increased in EMs compared to non-mycorrhizal roots. Higher CO2 assimilation, improved nutrient and carbohydrate status, and alleviated oxidative stress were found in mycorrhizal compared to non-mycorrhizal poplars despite higher Cd 2+ accumulation. These results indicate that mycorrhizas increase Cd 2+ uptake, probably by an enlarged root volume and overexpression of genes involved in Cd 2+ uptake and transport, and concurrently enhance Po. × canescens Cd tolerance by increased detoxification, improved nutrient and carbohydrate status and defence preparedness.

Association between blood cadmium levels and malnutrition in peritoneal dialysis

BMC Nephrology, 2014

Background: Malnutrition is associated with an increased risk of cardiovascular death and may cause protein-energy wasting in individuals with chronic kidney disease. A previous study demonstrated that blood cadmium levels (BCLs) were associated with malnutrition in maintenance hemodialysis (MHD) patients. However, the correlation between cadmium exposure and malnutrition remains unclear in chronic peritoneal dialysis (CPD) patients. This study examined the possible adverse effects of environmental cadmium exposure in CPD patients. Methods: A total of 301 CPD patients were enrolled and divided into 3 study groups based on the following BCL tertiles: low (<0.19 μg/L), middle (0.19-0.39 μg/L), and high (>0.39 μg/L). Demographic, hematological, biochemical, and dialysis-related data were obtained for analysis. The analysis also included values of nutritional and inflammatory markers. Results: The BCLs of CPD patients were lower than those of MHD patients. At baseline, patients in the high BCL group were older and had a higher prevalence of diabetes mellitus but lower serum albumin, creatinine, and phosphate levels than the patients in the other 2 groups. After adjusting for potential variables, stepwise backward multiple linear regression analysis revealed that age and alanine aminotransferase levels were positively associated with logarithmic transformation of BCLs (log BCLs), while serum albumin levels were negatively associated with log BCLs in CPD patients. The log BCLs were a significant determinant (beta coefficient ± standard error = −0.185 ± 0.074; P = 0.013) of nutritional status and significantly associated with the presence of malnutrition (odds ratio = 2.64; 95% confidence interval: 1.07-6.48; P = 0.035) in CPD patients after adjustment for related variables. Conclusions: BCL is significantly associated with nutritional status and malnutrition in CPD patients. Therefore, it is important for CPD patients to avoid environmental exposure to cadmium such as through smoking and consumption of cadmium-rich foods.

Cadmium-Induced Pathologies: Where Is the Oxidative Balance Lost (or Not)?

International Journal of Molecular Sciences, 2013

Over the years, anthropogenic factors have led to cadmium (Cd) accumulation in the environment causing various health problems in humans. Although Cd is not a Fenton-like metal, it induces oxidative stress in various animal models via indirect mechanisms. The degree of Cd-induced oxidative stress depends on the dose, duration and frequency of Cd exposure. Also the presence or absence of serum in experimental conditions, type of cells and their antioxidant capacity, as well as the speciation of Cd are important determinants. At the cellular level, the Cd-induced oxidative stress either leads to oxidative damage or activates signal transduction pathways to initiate defence responses. This balance is important on how different organ systems respond to Cd stress and ultimately define the pathological outcome. In this review, we highlight the Cd-induced oxidant/antioxidant status as well as the damage versus signalling scenario in relation to Cd toxicity. Emphasis is addressed to Cd-induced pathologies of major target organs, including a section on cell proliferation and carcinogenesis. Furthermore, attention is paid to Cd-induced oxidative stress in undifferentiated stem cells, which can provide information for future therapies in preventing Cd-induced pathologies.

Structural and functional alterations in photosynthetic apparatus of plants under cadmium stress

Botanical Studies, 2013

Cadmium is a potentially toxic heavy metal that hampers plant productivity by interfering with their photochemistry. Cd causes disturbances in a range of physiological processes of plants such as photosynthesis, water relations, ion metabolism and mineral uptake. Cd pronouncedly affects photosynthesis by alteration of its vital machinery in all aspects. Photosynthesis is a well organised and sequential process fundamental to all green plants and microorganisms which involves various components, including photosynthetic pigments and photosystems, the electron transport system and CO 2 reduction pathways. Any damage at any level caused by Cd, critically affects overall photosynthetic capacity. Present review focuses on key effects of Cd on photosynthetic apparatus including chloroplast structure, photosynthetic pigments, Chl-protein complexes and photosystems resulting in overall decrease in efficiency of carbon assimilation pathway.

The impact of environmental cadmium exposure on type 2 diabetes risk: a protocol for an overview of systematic reviews

Systematic Reviews

Background: Type 2 diabetes mellitus (T2DM) is a worldwide epidemic, and while its etiology is polygenic, the role of environmental contaminant exposure in T2DM pathogenesis is of increasing importance. However, the evidence presented in systematic reviews on the relationship between cadmium exposure and T2DM development is inconsistent. This overview aims to assess existing evidence from systematic reviews linking cadmium exposure to T2DM and select metabolic disorders in humans. Methods: Searches will be conducted in Medline, Embase, Web of Science, GEOBASE, BIOSIS Previews, and Cochrane Database of Systematic Reviews. Two reviewers (J.H and S.T.) will independently complete screening, data abstraction, risk of bias evaluation, and quality assessment. The primary outcome will be the association between cadmium exposure and T2DM prevalence. Secondary outcomes will include prediabetes, obesity, dyslipidemia, hypertension, and non-alcoholic fatty liver disease. We will perform a meta-analysis if two or more studies assess similar populations, utilize analogous methods, have related study designs, and evaluate similar outcomes. Discussion: This overview will assess current evidence from systematic reviews for the association between cadmium exposure and risk of T2DM and other metabolic morbidities. This overview may be helpful for policymakers and healthcare teams aiming to mitigate T2DM risk in populations at risk of cadmium exposure. Systematic review registration: PROSPERO CRD42019125956

Monensin ameliorates cadmium-induced hepatic injury in mice, subjected to subacute cadmium intoxication

Biotechnology & Biotechnological Equipment, 2014

This study was designed to evaluate the potential application of monensin as an oral drug for the treatment of cadmiuminduced hepatic dysfunction. The study was performed using ICR mouse model. Twenty-seven adult ICR male mice were divided into three groups of nine animals each: control (received distilled water and food ad libitum for 28 days); Cdintoxicated (treated orally with 20 mg/kg b.w. Cd(II) acetate from the 1st to the 14th day of the experimental protocol); and monensin treated group (intoxicated with Cd(II) acetate as described for the Cd-intoxicated group followed by an oral treatment with 16 mg/kg b.w. tetraethylammonium salt of monensic acid for two weeks). The obtained results demonstrated that the treatment of Cd-intoxicated animals with monensin restored the liver weight/body weight index to normal values, decreased the concentration of the toxic metal ion by 50% compared to the Cd-treated controls, and recovered the homeostasis of Cu and Zn. Monensin reduced the activity of aspartate aminotransferase, alanine aminotrasnferase and alkaline phosphatase in the plasma of Cd-treated animals to the normal control levels and ameliorated the Cd-induced inflammation in the liver. Taken together, these data demonstrated that monensin could be an effective chelating agent for the treatment of Cd-induced hepatotoxicity.

Urinary cadmium and mammographic density in premenopausal women

Breast Cancer Research and Treatment, 2011

Purpose-Mammographic density (MD), a strong marker of breast cancer risk, is influenced by genetic, environmental, and hormonal factors. Cadmium, a persistent and widespread environmental pollutant, has been associated with risk of breast cancer, and laboratory evidence suggests cadmium is a carcinogen in the breast. We investigated the hypothesis that cadmium exposure is associated with higher MD. Methods-In a cross-sectional study of MD and urinary cadmium concentration, percentage MD (MD%) and Breast Imaging-Reporting and Data Systems (BI-RADS ®) density category were determined from screening mammograms of 190 premenopausal women ages 40-45 years. Women completed a health questionnaire, and the cadmium content of spot urine samples was measured with inductively-coupled plasma mass spectrometry and corrected for urine creatinine. Urinary cadmium concentrations are thought to reflect exposure to cadmium over a period of 20-30 years. Multivariable linear regression and logistic regression were used to estimate the strength of association between urinary cadmium and mammographic breast density. Results-Adjusted mean MD% among women in the upper tertile of creatinine-corrected urine cadmium was 4.6% higher (95% confidence interval (CI): −2.3 to 11.6%) than in women in the lowest cadmium tertile. Each twofold increase in urine cadmium was associated with higher odds of MD% in the upper tertile (odds ratio(OR): 1.29, 95% CI: 0.82-2.02) or a BI-RADS category rating of "extremely dense" (OR: 1.75, 95% CI: 1.14-2.70). Stronger associations were observed among nulliparous women, and current or former smokers. Conclusions-Exposure to cadmium may be associated with increased breast density in premenopausal women.

Dietary Intake Estimates and Urinary Cadmium Levels in Danish Postmenopausal Women

PloS one, 2015

Cadmium is a known carcinogen that can disrupt endocrine signalling. Cigarette smoking and food are the most common routes of non-occupational exposure to cadmium. Cadmium accumulates in the kidney and can be measured in urine, making urine cadmium (U-Cd) a biomarker of long-term exposure. However dietary-cadmium (D-Cd) intake estimates are often used as surrogate indicator of cadmium exposure in non-smoking subjects. It is therefore important to investigate the concordance between D-Cd estimates obtained with Food Frequency Questionnaires and U-Cd. U-Cd levels were compared with estimated dietary-cadmium (D-Cd) intake in 1764 post-menopausal women from the Danish Diet, Cancer and Health cohort. For each participant, a food frequency questionnaire, and measures of cadmium content in standard recipes were used to judge the daily intake of cadmium, normalized by daily caloric intake. Cadmium was measured by ICP-MS in spot urine sampled at baseline and normalized by urinary creatinine....

Cadmium-induced cancers in animals and in humans

International journal of occupational and environmental health

Discovered in the early 1800s, the use of cadmium and various cadmium salts started to become industrially important near the close of the 19th century, rapidly thereafter began to flourish, yet has diminished more recently. Most cadmium used in the United States is a byproduct from the smelting of zinc, lead, or copper ores, and is used to manufacture batteries. Carcinogenic activity of cadmium was discovered first in animals and only subsequently in humans. Cadmium and cadmium compounds have been classified as known human carcinogens by the International Agency for Research on Cancer and the National Toxicology Program based on epidemiologic studies showing a causal association with lung cancer, and possibly prostate cancer, and studies in experimental animals, demonstrating that cadmium causes tumors at multiple tissue sites, by various routes of exposure, and in several species and strains. Epidemiologic studies published since these evaluations suggest that cadmium is also asso...

Endocrine Disrupting Chemicals and Endometrial Cancer: An Overview of Recent Laboratory Evidence and Epidemiological Studies

International Journal of Environmental Research and Public Health

Background: Although exposure to endocrine disruptor compounds (EDCs) has been suggested as a contributing factor to a range of women's health disorders including infertility, polycystic ovaries and the early onset of puberty, considerable challenges remain in attributing cause and effect on gynaecological cancer. Until recently, there were relatively few epidemiological studies examining the relationship between EDCs and endometrial cancer, however, in the last years the number of these studies has increased. Methods: A systematic MEDLINE (PubMed) search was performed and relevant articles published in the last 23 years (from 1992 to 2016) were selected. Results: Human studies and animal experiments are confirming a carcinogenic effect due to the EDC exposure and its carcinogenesis process result to be complex, multifactorial and long standing, thus, it is extremely difficult to obtain the epidemiological proof of a carcinogenic effect of EDCs for the high number of confusing factors. Conclusions: The carcinogenic effects of endocrine disruptors are plausible, although additional studies are needed to clarify their mechanisms and responsible entities. Neverthless, to reduce endocrine disruptors (ED) exposure is mandatory to implement necessary measures to limit exposure, particularly during those periods of life most vulnerable to the impact of oncogenic environmental causes, such as embryonic period and puberty.

Newborn sex-specific transcriptome signatures and gestational exposure to fine particles: findings from the ENVIRONAGE birth cohort

Environmental Health

Background: Air pollution exposure during pregnancy has been associated with adverse birth outcomes and health problems later in life. We investigated sex-specific transcriptomic responses to gestational long-and shortterm exposure to particulate matter with a diameter < 2.5 μm (PM 2.5) in order to elucidate potential underlying mechanisms of action. Methods: Whole genome gene expression was investigated in cord blood of 142 mother-newborn pairs that were enrolled in the ENVIRONAGE birth cohort. Daily PM 2.5 exposure levels were calculated for each mother's home address using a spatial-temporal interpolation model in combination with a dispersion model to estimate both long-(annual average before delivery) and short-(last month of pregnancy) term exposure. We explored the association between gene expression levels and PM 2.5 exposure, and identified modulated pathways by overrepresentation analysis and gene set enrichment analysis. Results: Some processes were altered in both sexes for long-(e.g. DNA damage) or short-term exposure (e.g. olfactory signaling). For long-term exposure in boys neurodevelopment and RhoA pathways were modulated, while in girls defensin expression was down-regulated. For short-term exposure we identified pathways related to synaptic transmission and mitochondrial function (boys) and immune response (girls). Conclusions: This is the first whole genome gene expression study in cord blood to identify sex-specific pathways altered by PM 2.5. The identified transcriptome pathways could provide new molecular insights as to the interaction pattern of early life PM 2.5 exposure with the biological development of the fetus.

Neuroprotective effect of quercetin against oxidative damage and neuronal apoptosis caused by cadmium in hippocampus

Toxicology and industrial health, 2013

The purpose of the present investigation was to evaluate cadmium (Cd)-induced neurotoxicity in hippocampal tissues and beneficial effect of quercetin (QE) against neuronal damage. A total of 30 male rats were divided into 3 groups: control, Cd-treated, and Cd + QE-treated groups. After the treatment, the animals were killed and hippocampal tissues were removed for biochemical and histopathological investigation. Cd significantly increased tissue malondialdehyde (MDA) and protein carbonyl (PC) levels and also decreased superoxide dismutase (SOD) and catalase (CAT) enzyme activities in hippocampal tissue compared with the control. Administration of QE with Cd significantly decreased the levels of MDA and PC and significantly elevated the levels of antioxidant enzymes in hippocampal tissue. In the Cd-treated group, the neurons of both tissues became extensively dark and degenerated with pyknotic nuclei. The morphology of neurons in Cd + QE group was well protected, but not as neurons o...

Levels of zinc, copper, cadmium, and lead in fruits and vegetables grown and consumed in Aseer Region, Saudi Arabia

Environmental Monitoring and Assessment, 2015

The levels of four metals (Zn, Cu, Cd, and Pb) were evaluated in two fruit types (apricot and fig), a fruity vegetable (tomato), and three leafy vegetables (arugula, spinach, and lettuce) that are commonly grown and consumed in Aseer Region, Saudi Arabia. Flame atomic absorption spectrophotometry was employed for quantification. The quality of results was checked by a certified reference material (NIST SRM 1570a). Good recovery values in the range of 87-104 % were achieved. Metals were quantified in washed and unwashed samples to evaluate the effect of washing. Statistically, no significant difference was noticed (p>0.05), except for Zn in arugula and Cu in apricot and spinach. The levels of metals found in the analyzed fruits and vegetables were in their normal ranges in crops and not posing any serious risks to the consumers in Aseer Region. The toxic elements Pb and Cd were well below the maximum levels set in the Saudi and international food standards. Zn and Cu levels were comparable to the ranges reported in worldwide previous studies.

Unboxing the molecular modalities of mutagens in cancer

Environmental Science and Pollution Research, 2021

The etiology of the majority of human cancers is associated with a myriad of environmental causes, including physical, chemical, and biological factors. DNA damage induced by such mutagens is the initial step in the process of carcinogenesis resulting in the accumulation of mutations. Mutational events are considered the major triggers for introducing genetic and epigenetic insults such as DNA crosslinks, single-and double-strand DNA breaks, formation of DNA adducts, mismatched bases, modification in histones, DNA methylation, and microRNA alterations. However, DNA repair mechanisms are devoted to protect the DNA to ensure genetic stability, any aberrations in these calibrated mechanisms provoke cancer occurrence. Comprehensive knowledge of the type of mutagens and carcinogens and the influence of these agents in DNA damage and cancer induction is crucial to develop rational anticancer strategies. This review delineated the molecular mechanism of DNA damage and the repair pathways to provide a deep understanding of the molecular basis of mutagenicity and carcinogenicity. A relationship between DNA adduct formation and cancer incidence has also been summarized. The mechanistic basis of inflammatory response and oxidative damage triggered by mutagens in tumorigenesis has also been highlighted. We elucidated the interesting interplay between DNA damage response and immune system mechanisms. We addressed the current understanding of DNA repair targeted therapies and DNA damaging chemotherapeutic agents for cancer treatment and discussed how antiviral agents, antiinflammatory drugs, and immunotherapeutic agents combined with traditional approaches lay the foundations for future cancer therapies.

Cadmium exposure and MEG3 methylation differences between Whites and African Americans in the NEST Cohort

Environmental Epigenetics, 2019

Cadmium (Cd) is a ubiquitous environmental pollutant associated with a wide range of health outcomes including cancer. However, obscure exposure sources often hinder prevention efforts. Further, although epigenetic mechanisms are suspected to link these associations, gene sequence regions targeted by Cd are unclear. Aberrant methylation of a differentially methylated region (DMR) on the MEG3 gene that regulates the expression of a cluster of genes including MEG3, DLK1, MEG8, MEG9 and DIO3 has been associated with multiple cancers. In 287 infant–mother pairs, we used a combination of linear regression and the Getis-Ord Gi* statistic to determine if maternal blood Cd concentrations were associated with offspring CpG methylation of the sequence region regulating a cluster of imprinted genes including MEG3. Correlations were used to examine potential sources and routes. We observed a significant geographic co-clustering of elevated prenatal Cd levels and MEG3 DMR hypermethylation in cor...

Racial disparities in liver cancer: Evidence for a role of environmental contaminants and the epigenome

Frontiers in Oncology

Liver cancer incidence has tripled since the early 1980s, making this disease one of the fastest rising types of cancer and the third leading cause of cancer-related deaths worldwide. In the US, incidence varies by geographic location and race, with the highest incidence in the southwestern and southeastern states and among racial minorities such as Hispanic and Black individuals. Prognosis is also poorer among these populations. The observed ethnic disparities do not fully reflect differences in the prevalence of risk factors, e.g., for cirrhosis that may progress to liver cancer or from genetic predisposition. Likely substantial contributors to risk are environmental factors, including chemical and non-chemical stressors; yet, the paucity of mechanistic insights impedes prevention efforts. Here, we review the current literature and evaluate challenges to reducing liver cancer disparities. We also discuss the hypothesis that epigenetic mediators may provide biomarkers for early det...

Diallyl disulfide attenuation effect on transcriptome in rat liver cells against cadmium chloride toxicity

Environmental Toxicology, 2019

In this report, liver cells were treated with cadmium chloride (CdCl 2) and diallyl disulfide (DADS), a major compound from garlic to attenuate the toxic effect of Cd on transcriptome. The viability of Cd treated cells was reduced to 19.9% ± 2.4% in comparison to the untreated cells, whereas the viability of DADS pretreated cells was increased to 48.6% ± 2%. The attenuation effect of DADS was studied at shorter period (6 hours). Transcriptome analysis of CdCl 2 alone treated cells resulted in 2119 and 982 (up and down) regulated genes (≥ 2 or ≤ 2-fold), whereas pretreated cells with DADS resulted in 2597 and 1784 genes. These genes were known to function in many important biological processes. Affymetrix array analysis was validated by the pathway specific PCR array that exhibited the same trend of expression. The current study clearly shows the DADS attenuation effect on transcriptome in CdCl 2treated rat liver cells.

Effects of Cadmium on Bioaccumulation, Bioabsorption, and Photosynthesis in Sarcodia suiae

International Journal of Environmental Research and Public Health, 2020

This study investigated the changes in bioaccumulation, bioabsorption, photosynthesis rate, respiration rate, and photosynthetic pigments (phycoerythrin, phycocyanin, and allophycocyanin) of Sarcodia suiae following cadmium exposure within 24 h. The bioabsorption was significantly higher than the bioaccumulation at all cadmium levels (p < 0.05). The ratios of bioabsorption/bioaccumulation in light and dark bottles were 2.17 and 1.74, respectively, when S. suiae was exposed to 5 Cd2+ mg/L. The chlorophyll a (Chl-a) concentration, oxygen evolution rate (photosynthetic efficiency), and oxygen consumption rate (respiratory efficiency) decreased with increasing bioaccumulation and ambient cadmium levels. The levels of bioaccumulation and bioabsorption in light environments were significantly higher than those in dark environments (p < 0.05). In addition, the ratios of phycoerythrin (PE)/Chl-a, phycocyanin (PC)/Chl-a, and allophycocyanin (APC)/Chl-a were also higher in light bottles...

Integrating Environment and Aging Research: Opportunities for Synergy and Acceleration

Frontiers in Aging Neuroscience, 2022

Despite significant overlaps in mission, the fields of environmental health sciences and aging biology are just beginning to intersect. It is increasingly clear that genetics alone does not predict an individual’s neurological aging and sensitivity to disease. Accordingly, aging neuroscience is a growing area of mutual interest within environmental health sciences. The impetus for this review came from a workshop hosted by the National Academies of Sciences, Engineering, and Medicine in June of 2020, which focused on integrating the science of aging and environmental health research. It is critical to bridge disciplines with multidisciplinary collaborations across toxicology, comparative biology, epidemiology to understand the impacts of environmental toxicant exposures and age-related outcomes. This scoping review aims to highlight overlaps and gaps in existing knowledge and identify essential research initiatives. It begins with an overview of aging biology and biomarkers, followe...

The Role of Cadmium and Nickel in Estrogen Receptor Signaling and Breast Cancer: Metalloestrogens or Not?

Journal of Environmental Science and Health, Part C, 2012

During the last half-century, incidences of breast cancer have increased globally. Various factors-genetic and environmental-have been implicated in the initiation and progression of this disease. One potential environmental risk factor that has not received a lot of attention is the exposure to heavy metals. While several mechanisms have been put forth describing how high concentrations of heavy metals play a role in carcinogenesis, it is unclear whether chronic, lowlevel exposure to certain heavy metals (i.e. cadmium and nickel), can directly result in the development and progression of cancer. Cadmium and nickel have been hypothesized to play a role in breast cancer development by acting as metalloestrogens-metals that bind to estrogen receptors and mimic the actions of estrogen. Since the lifetime exposure to estrogen is a wellestablished risk factor for breast cancer, anything that mimics its activity will likely contribute to the etiology of the disease. However, heavy metals, depending on their concentration, are capable of binding to a variety of proteins and may exert their toxicities by disrupting multiple cellular functions, complicating the analysis of whether heavy metal-induced carcinogenesis is mediated by the estrogen receptor. The purpose of this review is to discuss the various epidemiological, in vivo, and in vitro studies that show a link between the heavy metals, cadmium and nickel, and breast cancer development. We will particularly focus on the studies that test whether or not these two metals act as metalloestrogens in order to assess the strength of the data supporting this hypothesis.

Association Between Serum Cadmium and Arsenic Levels with Bladder Cancer: A Case-control Study

International Journal of Cancer Management, 2021

Background: Bladder cancer is the second most common cancer of the genitourinary system and the eighth cause of cancer death. In addition to known risk factors such as smoking and urinary stones, trace elements are also effective in causing bladder cancer and other cancers. Objectives: This study was conducted to determine the association between bladder cancer and the carcinogens cadmium and arsenic. Methods: This case-control study was conducted on 40 patients with bladder cancer admitted to Shahid Bahonar Hospital and a control group of 40 healthy individuals in Kerman, Iran, in 2018. The serum levels of arsenic and cadmium were measured by atomic absorptiometry. The paired t-test and chi-square tests were employed to assess the difference between cases and controls groups. An unadjusted and 2 multivariable conditional regression models were separately adjusted on sex, family cancer history, residence, occupation, and smoking and were used to estimate odds ratios (OR) and 95% con...

Nano-sized magnetic Ni particles based dispersive solid-phase extraction of trace Cd before the determination by flame atomic absorption spectrometry with slotted quartz tube: a new, accurate, and sensitive quantification method

Environmental Monitoring and Assessment, 2020

In this study, a new analytical strategy was developed to determine trace cadmium in aqueous samples with high sensitivity and accuracy. A combination of magnetic nickel nanoparticles (Ni-MNPs) based dispersive solid-phase extraction (DSPE) and flame atomic absorption spectrometry fitted with a slotted quartz tube (SQT-FAAS) lowered the detection limit of cadmium. The magnetic Ni nanoparticles were synthesized, characterized, and thoroughly optimized in a stepwise approach. The quartz tube was custom cut in the laboratory to suit the specifics of the flame burner. Using the optimized conditions, a limit of detection value of 0.58 μg/L and limit of quantification value of 1.93 μg/L were obtained. To demonstrate accuracy and applicability of the developed method, well water samples were analyzed for their Cd content, and matrix effect on the extraction yield was investigated. The percent recovery results calculated ranged from 93.8 to 108.2%, with corresponding standard deviation values ranging from 1.7 to 7.7. These results established the developed method as sensitive, accurate, and precise for determination of cadmium at trace levels.

Genome-wide association analysis and QTL mapping reveal the genetic control of cadmium accumulation in maize leaf

BMC genomics, 2018

Accumulation of cadmium (Cd) in maize (Zea mays L.) poses a significant risk to human health as it is ingested via the food chain. A genome-wide association study (GWAS) was conducted in a population of 269 maize accessions with 43,737 single nucleotide polymorphisms (SNPs) to identify candidate genes and favorable alleles for controlling Cd accumulation in maize. When grown in contaminated soil, accessions varied significantly in leaf Cd concentration at both the seeding and maturing stages with phenotypic variation and the coefficient of variation all above 48%. The co-localized region between SYN27837 (147,034,650 bp) and SYN36598 (168,551,327 bp) on chromosome 2 was associated with leaf Cd under three soil conditions varying in Cd content in 2015 and 2016. The significant SNP (SYN25051) at position 161,275,547 could explained 27.1% of the phenotype variation. Through QTL mapping using the IBMSyn10 double haploid (DH) population, we validated the existence of a major QTL identifi...

Breeding for low cadmium barley by introgression of a Sukkula-like transposable element

Nature Food, 2020

Barley is the fourth most produced cereal crop in the world and one of the major dietary sources of cadmium (Cd), which poses serious threats to human health. Here, we identify a gene that encodes a P-type heavy metal ATPase 3 (HvHMA3) responsible for grain Cd accumulation in barley. HvHMA3 from the high Cd barley variety Haruna Nijo in Japan and the low Cd variety BCS318 in Afghanistan shared 97% identity at the amino acid level. In addition, the HvHMA3 from both varieties showed similar transport activity for Cd and the same subcellular localization at the tonoplast. However, the expression of HvHMA3 was double in BCS318 than in Haruna Nijo. A 3.3-kilobase Sukkula-like transposable element was found to be inserted upstream of the gene in the low Cd variety, which functioned as a promoter and enhanced the expression of HvHMA3. Introgression of this insertion to an elite barley cultivar through backcrossing resulted in decreased Cd accumulation in the grain grown in Cd-contaminated soil without yield penalty. The decreased Cd accumulation resulting from the insertion was also found in some other barley landraces in the world. Our results indicate that insertion of the Sukkula-like transposable element plays an important role in upregulating HvHMA3 expression.

Trans-resveratrol Inhibits Tau Phosphorylation in the Brains of Control and Cadmium Chloride-Treated Rats by Activating PP2A and PI3K/Akt Induced-Inhibition of GSK3β

Neurochemical Research, 2018

This study investigated if resveratrol (RES) can protect against cadmium chloride (CdCl 2)-induced memory loss and Tau protein hyperphosphorylation in rats and explored its effect on AMPK/PI3K/Akt signaling pathway. Rats (n = 10/group) were divided into seven groups as: control; control + DMSO; control + LY294002, a selective PI3K inhibitor (0.25 µg/100 g, i.p); control + RES (300 mg/kg, orally); CdCl 2 (5 mg/kg, orally); CdCl 2 + RES and CdCl 2 + RES + LY294002. All treatments were carried out for 30 consecutive days on a daily basis. RES improved both short and long-term memory as analyzed by novel object recognition task and significantly increased brain levels of glutathione in both control and CdCl 2-treated rats. It also inhibited ROS levels of malondialdehyde in the brains of CdCl 2-treated rats. In both groups, RES decreased the phosphorylation rate of Tau at Ser 199 and Ser 296. Concomitantly, it significantly increased protein levels of p-GSK3β (Ser9) and p-PP2A and decreased p-GSK3β (Tyr 216). Also, RES activated PI3K/Akt signaling pathway in both control and CdCl 2 treated rats by increasing levels of p-PI3K (Tyr 607) and p-Akt (Ser 473). This was concomitant with significant increase in the levels of AMPK and p-AMPK, known upstream regulators of PI3K/Akt signaling pathway. Interestingly, all the above listed beneficial effects of RES, except their effect on AMPK/p-AMPK, were completely abolished in CdCl 2 + RES + LY294002-treated rats. In conclusion, in addition to its antioxidant potential, RES inhibits Tau phosphorylation in rat's brain by activating PP2A protein and AMPK/PI3K/Akt-induced inhibition of GSK3β.

Synergistic effect of silicon and selenium on the alleviation of cadmium toxicity in rice plants

Journal of Hazardous Materials, 2021

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Metal-induced oxidative stress and plant mitochondria

International Journal of Molecular Sciences, 2011

A general status of oxidative stress in plants caused by exposure to elevated metal concentrations in the environment coincides with a constraint on mitochondrial electron transport, which enhances ROS accumulation at the mitochondrial level. As mitochondria are suggested to be involved in redox signaling under environmental stress conditions, mitochondrial ROS can initiate a signaling cascade mediating the overall stress response, i.e., damage versus adaptation. This review highlights our current understanding of metal-induced responses in plants, with focus on the production and detoxification of mitochondrial ROS. In addition, the potential involvement of retrograde signaling in these processes will be discussed.

Mitogen-Activated Protein (MAP) Kinases in Plant Metal Stress: Regulation and Responses in Comparison to Other Biotic and Abiotic Stresses

International Journal of Molecular Sciences, 2012

Exposure of plants to toxic concentrations of metals leads to disruption of the cellular redox status followed by an accumulation of reactive oxygen species (ROS). ROS, like hydrogen peroxide, can act as signaling molecules in the cell and induce signaling via mitogen-activated protein kinase (MAPK) cascades. MAPK cascades are evolutionary conserved signal transduction modules, able to convert extracellular signals to appropriate cellular responses. In this review, our current understanding about MAPK signaling in plant metal stress is discussed. However, this knowledge is scarce compared to research into the role of MAPK signaling in the case of other abiotic and biotic stresses. ROS production is a common response induced by different stresses and undiscovered analogies may exist with metal stress. Therefore, further attention is given to MAPK signaling in other biotic and abiotic stresses and its interplay with other signaling pathways to create a framework in which the involvement of MAPK signaling in metal stress may be studied.

Unraveling the effects of arbuscular mycorrhizal fungi on cadmium uptake and detoxification mechanisms in perennial ryegrass (Lolium perenne)

Science of The Total Environment, 2021

Phragmites australis (Cav.) Trin. ex Steud. has been reported to form a symbiosis with arbuscular mycorrhizal fungus (AMF). However, the tolerance mechanism for AMF symbiosis on cadmium (Cd) phytotoxicity still remains unclear. In this study, we investigated the effects of Rhizophagus irregularis inoculation on Cd-stressed (0, 1, and 20 mg L −1) roots, stems, and leaves of P. australis with regard to subcellular Cd distribution and chemical forms of Cd. In addition, transmission electron microscopy and Fourier transform infrared spectroscopy were used to investigate variations in subcellular structures and functional groups in plant organs. The results showed that AMF inoculation could induce selective Cd distribution at subcellular levels, depending on different Cd treatments. The investigation of the chemical forms illustrated that AMF inoculation could alleviate Cd toxicity in all organs. Increases were observed in the ratios of undissolved Cd (F HAc) and oxalate Cd (F HCl), while decreases were observed in pectates and protein-integrated Cd (F NaCl) as well as water soluble Cd (F W). Hydroxyl (-OH), amide (-NH), carboxyl (C=O), and phosphate (P=O) groups as well as CO and C-N stretching played predominant roles for the enhancement of Cd tolerance in response to AMF inoculation. These results provide instructive evidence for the mechanisms by which AMF inoculation enhances the Cd tolerance of P. australis via Cd uptake and distribution.

N2S2 pyridinophane-based fluorescent chemosensors for selective optical detection of Cd2+ in soils

New Journal of Chemistry, 2020

Herein we describe the synthesis and coordination properties in solution towards Zn2+ and Cd2+ of the ligands L1 and L2 containing the 2,8-dithia-5-aza-2,6-pyridinophane (L) macrocyclic receptor unit and the 2-(2′-hydroxy-3′-naphthyl)-4-methylbenzoxazole (HNBO) or 7-(2ethylamino)-4-methylcoumarin chromophores. Spectrophotometric and spectrofluorimetric measurements in the UV-Visible region (MeCN/H2O solution 4:1 v/v) and 1H NMR measurements provided insight into the nature of complex species and transduction mechanisms responsible for the optical responses. The ligands showed an OFF-ON response upon addition of Zn2+ and Cd2+, for L1, and only Cd2+, for L2, in both cases attributable to the formation of 1:1 metal-to-ligand complexes. The crystal structure of [CdL2(NO3)2] is reported, being Cd2+ heptacoordinated by L and NO3anions in a N2S2O3 environment. Exploiting the fluorescence properties of L1 and L2, an optical sensor array was developed featuring PVC membranes containing the dispersed sensing material and based on the Photoassisted Technique (PT) for signal acquisition, which allowed a quantitative determination of Cd2+ in real samples (soils). All phases from the design of the chemosensors to the development of the sensing device are discussed.