Genotoxic Effect of Atrazine, Arsenic, Cadmium and Nitrate, Individually and in Mixtures at Maximum Contaminant Levels on mammalian Breast Cell Lines (original) (raw)
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In-Vivo and In-Vitro Study of the Relation Between Cadmium and Breast Cancer by
Cadmium is a potent carcinogenic environmental pollutant that has been lastly linked to breast cancer. This research was done to find out the role of cadmium in induction of breast cancer both in-vivo and in-vitro. In-vivo study was conducted on 100 female patients who were randomly chosen from those attending Oncology Center, Mansoura University. Cadmium concentration was measured in urinary and tissue samples from 75 patients with breast cancer (test group) and 25 patients with benign breast diseases (positive control group), using inductive coupled plasma (ICP)-spectrometer. In-vitro study included primary cultured normal mammary cells that were divided into test group (treated with CdCl 2 at a concentration of 15µM) and a matched control group (untreated cultured mammary cells). Cell viability and bleomycin dependent DNA damage were evaluated. In-vivo study shows significant increases in urinary and tissue cadmium concentrations in breast cancer patients compared to their corresponding controls (p=0.000). Regarding in-vitro study, significant reduction in cell viability associated with significant increase in DNA damage were observed (p<0.05). It could be concluded that the present study posits a causal association between cadmium exposure and breast cancer.
Emerging Contaminants, 2016
The incidence of breast cancer is on a rise worldwide; it is a disease having a complex etiology. Besides genetics, environmental and other lifestyle factors play a role in the development of the disease. There has been a keen interest in studying associations between breast cancer and exposures to emerging environmental chemicals, which mimic estrogens or influence estrogen levels and signaling in the human body. The common consequence of an endocrine disrupting chemical exposure is that it may have an impact on breast cancer etiology by stimulating formation as well as progression of breast cancer. Exposures to selected emerging environmental contaminants such as alkylphenols (APs), bisphenol A (BPA), parabens, perfluoroalkyl substances (PFASs), phthalates, polybrominated diphenyl ethers (PBDEs), synthetic musks and triclosan, and their probable role in breast cancer development are reviewed. Studies evaluated include the experimental in vitro and in vivo studies as well as human population based studies. In vitro and in vivo evidences indicate that a number of emerging environmental contaminants may play a role in the initiation and/or progression of breast cancer. Although exposures have been assessed in some human populations, breast and other cancer risks associated with these exposures are largely unknown. Efforts should be focussed on the evaluation of these environmental exposures in human populations and their interactions with each other and other genetic and lifestyle risk factors.
Archives of Environmental Contamination and Toxicology, 1998
A human breast cancer cell line (MCF-7) was used to develop an in vitro screening assay for the detection of xenoestrogenic environmental pollutants. MCF-7 cells were cultured in DMEM containing 5% fetal bovine serum (FBS). An estrogenic response was defined as an increase in the frequency of proliferating MCF-7 cells, and was measured using a thymidine analog, bromodeoxyuridine, and flow cytometry. Di-2-ethylhexyl phthalate (DEHP) and 4-n-nonylphenol (4-n-NP) were used as model chemicals. The proliferation rate of S-phase cells after 24 h of exposure to various concentrations of 17-estradiol and to model compounds was compared with a positive and a negative control, containing 1 nM 17-estradiol and 0.1% ethanol, respectively. DEHP and 4-n-NP increased the frequency of proliferating MCF-7 cells in a dose-dependent manner. The lowest concentration that significantly increased the proliferation of MCF-7 cells was 10 µM for DEHP and 1 µM for 4-n-NP. The results showed that the assay is accurate and quick to perform. It may prove a valuable tool for screening potential estrogen-mimicking environmental pollutants.
2020
Recently, soluble forms of aluminum for human use or consumption have been determined to be potentially toxic due to their association with hepatic, neurological, hematological, neoplastic, and bone conditions. This study aims to assess the genotoxic effect of aluminum chloride on genomic instability associated with the onset of N-nitroso-N-methylurea (NMU)-induced breast cancer in Sprague Dawley rats. The dietary behavior of the rats was assessed, and the concentration of aluminum in the mammary glands was determined using atomic absorption spectroscopy. Genomic instability was determined in the histological sections of mammary glands stained with hematoxylin and eosin. Moreover, micronucleus in peripheral blood and comet assays were performed. The results of dietary behavior evaluation indicated no significant differences between the experimental treatments. However, aluminum concentration in breast tissues was high in the +2000Al/−NMU treatment. This experimental treatment caused...
Environmental contaminants in pathogenesis of breast cancer
Indian journal of experimental biology, 2006
This review is an attempt to comprehend the diverse groups of environmental chemical contaminants with a potential for pathogenesis of breast cancer, their probable sources and the possible mechanisms by which these environmental contaminants act and interplay with other risk factors. Estrogens are closely related to the pathogenesis of breast cancer. Oxidative catabolism of estrogen, mediated by various cytochrome P450 enzymes, generates reactive free radicals that can cause oxidative damage. The same enzymes of estrogenic metabolic pathways catalyze biological activation of several environmental (xenobiotic) chemicals. Xenobiotic chemicals may exert their pathological effects through generation of reactive free radicals. Breast tissue can be a target of several xenobiotic agents. DNA-reactive metabolites of different xenobiotic compounds have been detected in breast tissue. Many phase I and II xenobiotic metabolizing enzymes are expressed in both normal and cancerous breast tissue...
In vivo xenoestrogenic actions of cadmium and arsenic in anterior pituitary and uterus
Reproduction (Cambridge, England), 2016
Cadmium (Cd) and arsenic (iAs) are toxic metals ubiquitously present in the environment. Both pollutants exert nonmonotonic dose responses, being mostly cytotoxic at high concentrations but mimicking estrogen (E2) effects at low doses. Xenoestrogenic activity of Cd and iAs has been demonstrated in different hormone-dependent tumor cell lines; however, their actions in vivo remain largely unknown. Here, we investigated whether in vivo administration of low doses of Cd and iAs through drinking water would display xenoestrogenic effects in the anterior pituitary gland and uterus of ovariectomized rats. Cd (1ppm) and iAs (0.1ppm) exposure increased the wet weight of anterior pituitary gland and uterus and induced proestrus- and estrus-like vaginal smears. Both metals stimulate cell proliferation of these tissues as they increased the expression of proliferation markers. More importantly, they augmented soluble guanylyl cyclase α1 subunit expression, which has been linked to hormone-depe...
Toxicological Sciences, 2007
Human exposure to arsenic (As) has become an important public health concern. Exposures most commonly occur through consumption of drinking water where the current maximum contaminant level of As, set by the U.S. Environmental Health Administration and the World Health Organization, is 10 lg/l. However, contamination from natural sources in various areas of the United States such as New England and the Southwest, and regions of the world, such as Bangladesh and Taiwan can reach hundreds of micrograms/ liter in wells. Exposures can also occur in occupational settings where arsenic is used to manufacture pesticides and wood preservatives, and superfund sites where industrial waste was disposed. An example of the issue and concern is represented by this recent headline which appeared in the Baltimore Sun on Friday, 20 April 2007. ''ARSENIC FORCES CLOSING OF PARK-Tests show high levels in soil; city locks gates of Swann Park.'' Swann Park is located next to a site where arsenic was used in the manufacture of pesticides. Exposure to high levels of As has been associated with various human diseases including cardiovascular and diabetes, and cancers of the skin, lung, bladder, kidney, and liver (see reviews by Huang et al., 2004; Rossman, 2003; Tapio and Grosche, 2006). Recent systematic reviews of the epidemiologic evidence for associations of As exposure with cardiovascular disease (Navas-Acien et al., 2005) and diabetes (Navas-Acien et al., 2006) detected increased risks associated with the highest As exposure categories in Taiwan, but were inconclusive in other populations. While the Taiwan studies suffered from several methodological limitations that made exposure estimates uncertain, the observations from these studies indicate the importance of conducting additional, well-designed investigations. In New Hampshire, where drinking water levels are commonly elevated, an association was observed between the highest category of As exposure, as determined by As levels in toenail clippings, and bladder
Journal of Chemical Health Risks, 2017
The hazardous consequences of heavy metal ions (HMIs) on human health necessitate the immediate need to probe fundamentally the interactions and cytotoxic effects of HMIs on humans. This study investigated the influence of five toxic HMIs (arsenic (As (III)), cadmium (Cd (II)), chromium (Cr (VI)), mercury (Hg (II)), and lead (Pb (II))) on human TNBC (HCC 1806) cell viability using optical microscopy, trypan blue dye-exclusion assays, and flow cytometry. The TNBC cells were exposed to varying concentrations of HMIs for 24 and 48 hours. We evaluated the influence of the concentrations and duration of HMIs exposure on TNBC cell viability. Light microscopy, cell viability assays, revealed that after 48-hour treatment of TNBC cells with 1 x 10-5 M of As (III), Cd (II), Hg (II), Cr (IV), and Pb (II) resulted in cell viabilities of 23%, 34%, 35%, 56%, 91% respectively, suggesting that As (III) has the greatest cytotoxicity (77% cell death) while Pb (II) showed the least (9% cell death). Fu...
Genotoxic potential of arsenic at its reference dose
Ecotoxicology and Environmental Safety, 2012
Arsenic, a highly hazardous contaminant in our drinking water, accounts for various toxic effects (including cancer) in human. However, intake of arsenic @0.3 mg kg À 1 day À 1 through drinking water, containing arsenic at its guideline value or maximum contaminant limit (10 mg L À 1), has been estimated to pose very little or no measurable risk to cancer in humans. The value also appears to be equal to the human reference dose (or index dose) of arsenic based on human skin toxicity data. The present work was a quantitative assessment of the genotoxic potential of arsenic in mice at doses equivalent to its human reference dose as well as its multiples. Significant increases in the frequencies of chromosome abnormalities in the bone marrow cells were registered over the control level upon exposure to all the doses of arsenic including its reference dose (or index dose). The assessment of arsenic genotoxicity in humans at low doses will therefore be highly instrumental in establishing a permissible limit of arsenic in drinking water.