Perspectives on the mechanism of nickel carcinogenesis gained from models of in vitro carcinogenesis (original) (raw)
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Carcinogenicity Assessment of Selected Nickel Compounds
Toxicology and Applied Pharmacology, 1997
Advisory Document (EPA, 1986). As a result of this project, Carcinogenicity Assessment of Selected Nickel Compounds. the International Committee on Nickel Carcinogenesis in OLLER, A. R., COSTA, M., AND OBERDÖ RSTER, G. (1997). Toxicol. Man (ICNCM) was formed (as a joint effort between indus-Appl. Pharmacol. 143, 152-166.
Toxics, 2013
Nickel is a well-known human lung carcinogen with the particulate form being the most potent; however, the carcinogenic mechanism remains largely unknown. Few studies have investigated the genotoxicity and carcinogenicity of nickel in its target cell, human bronchial epithelial cells. Thus, the goal of this study was to investigate the effects of particulate nickel in human lung epithelial cells. We found that nickel subsulfide induced concentration-and time-dependent increases in both cytotoxicity and genotoxicity in human lung epithelial cells (BEP2D). Chronic exposure to nickel subsulfide readily induced cellular transformation, inducing 2.55, 2.9 and 2.35 foci per dish after exposure to 1, 2.5 and 5 μg/cm 2 nickel subsulfide, respectively. Sixty-one, 100 and 70 percent of the foci isolated from 1, 2.5, and 5 μg/cm 2 nickel subsulfide treatments formed colonies in soft agar and the degree of soft agar colony growth increased in a concentration-dependent
Nickel essentiality, toxicity, and carcinogenicity
Critical Reviews in Oncology Hematology, 2002
The increasing utilization of heavy metals in modern industries leads to an increase in the environmental burden. Nickel represents a good example of a metal whose use is widening in modern technologies. As the result of accelerated consumption of nickel-containing products nickel compounds are released to the environment at all stages of production and utilization. Their accumulation in the environment may represent a serious hazard to human health. Among the known health related effects of nickel are skin allergies, lung fibrosis, variable degrees of kidney and cardiovascular system poisoning and stimulation of neoplastic transformation. The mechanism of the latter effect is not known and is the subject of detailed investigation. This review provides an analysis of the current state in the field.
Reviews on Environmental Health, 2011
Nickel, a naturally occurring element that exists in various mineral forms, is mainly found in soil and sediment, and its mobilization is influenced by the physicochemical properties of the soil. Industrial sources of nickel include metallurgical processes such as electroplating, alloy production, stainless steel, and nickel-cadmium batteries. Nickel industries, oil-and coal-burning power plants, and trash incinerators have been implicated in its release into the environment. In humans, nickel toxicity is influenced by the route of exposure, dose, and solubility of the nickel compound. Lung inhalation is the major route of exposure for nickel-induced toxicity. Nickel may also be ingested or absorbed through the skin. The primary target organs are the kidneys and lungs. Other organs such as the liver, spleen, heart and testes may also be affected to a lesser extent. Although the most common health effect is an allergic reaction, research has also demonstrated that nickel is carcinogenic to humans. The focus of the present review is on recent research concerning the molecular mechanisms of nickel-induced genotoxicity and carcinogenicity. We first present a background on the occurrence of nickel in the environment, human exposure, and human health effects.
Oxidative DNA damage in cultured cells and rat lungs by carcinogenic nickel compounds
Free Radical Biology and Medicine, 2001
DNA damage in cultured cells and in lungs of rats induced by nickel compounds was investigated to clarify the mechanism of nickel carcinogenesis. DNA strand breaks in cultured cells exposed to nickel compounds were measured by using a pulsed field gel electrophoresis technique. Among nickel compounds (Ni 3 S 2 , NiO (black), NiO (green), and NiSO 4 ), only Ni 3 S 2 , which is highly carcinogenic, induced lesions of both double-and single-stranded DNA in cultured human cells (Raji and HeLa cells). Treatment of cultured HeLa cells with Ni 3 S 2 (10 g/ml) induced a 1.5-fold increase in 8-hydroxy-2Ј-deoxyguanosine (8-OH-dG) compared with control, whereas NiO (black), NiO (green), and NiSO 4 did not enhance the generation of 8-OH-dG. Intratracheal instillation of Ni 3 S 2 , NiO(black), and NiO(green) to Wistar rats increased 8-OH-dG in the lungs significantly. NiSO 4 induced a smaller but significant increase in 8-OH-dG. Histological studies showed that all the nickel compounds used induced inflammation in lungs of the rats. Nitric oxide (NO) generation in phagocytic cells induced by Ni 3 S 2 , NiO(black), and NiO(green) was examined using macrophage cell line RAW 264.7 cells. NO generation in RAW 264.7 cells stimulated with lipopolysaccharide was enhanced by all nickel particles. Two mechanisms for nickel-induced oxidative DNA damage have been proposed as follows: all the nickel compounds used induced indirect damage through inflammation, and Ni 3 S 2 also showed direct oxidative DNA damage through H 2 O 2 formation. This double action may explain relatively high carcinogenic risk of Ni 3 S 2 .
Molecular Mechanisms of Nickel Carcinogenesis
Annual Review of Pharmacology and Toxicology, 1991
Humans are exposed to carcinogenic nickel (Ni) compounds both occupationally and environmentally. In this paper, molecular mechanisms of nickel carcinogenesis are considered from the point-of-view of the uptake of nickel sulfide particles in cells, their dissolution and their effects on heterochromatin. Molecular mechanisms by which nickel induces gene silencing, DNA hypermethylation and inhibition of histone acetylation, will be discussed.
Respiratory carcinogenicity assessment of soluble nickel compounds
Environmental Health Perspectives, 2002
The many chemical forms of nickel differ in physicochemical properties and biological effects. Health assessments for each main category of nickel species are needed. The carcinogenicity assessment of water-soluble nickel compounds has proven particularly difficult. Epidemiologic evidence indicates an association between inhalation exposures to nickel refinery dust containing soluble nickel compounds and increased risk of respiratory cancers. However, the nature of this association is unclear because of limitations of the exposure data, inconsistent results across cohorts, and the presence of mixed exposures to water-insoluble nickel compounds and other confounders that are known or suspected carcinogens. Moreover, well-conducted animal inhalation studies, where exposures were solely to soluble nickel, failed to demonstrate a carcinogenic potential. Similar negative results were seen in animal oral studies. A model exists that relates respiratory carcinogenic potential to the bioavailability of nickel ion at nuclear sites within respiratory target cells. This model helps reconcile human, animal, and mechanistic data for soluble nickel compounds. For inhalation exposures, the predicted lack of bioavailability of nickel ion at target sites suggests that water-soluble nickel compounds, by themselves, will not be complete human carcinogens. However, if inhaled at concentrations high enough to induce chronic lung inflammation, these compounds may enhance carcinogenic risks associated with inhalation exposure to other substances. Overall, the weight of evidence indicates that inhalation exposure to soluble nickel alone will not cause cancer; moreover, if exposures are kept below levels that cause chronic respiratory toxicity, any possible tumor-enhancing effects (particularly in smokers) would be avoided.
Regulatory Toxicology and Pharmacology, 2003
Increased lung and nasal cancer risks have been reported in several cohorts of nickel refinery workers, but in more than 90% of the nickel-exposed workers that have been studied there is little, if any evidence of excess risk. This investigation utilizes human exposure measurements, animal data from cancer bioassays of three nickel compounds, and a mechanistic theory of nickel carcinogenesis to reconcile the disparities in lung cancer risk among nickel-exposed workers. Animal data and mechanistic theory suggest that the apparent absence of risk in workers with low nickel exposures is due to threshold-like responses in lung tumor incidence (oxidic nickel), tumor promotion (soluble nickel), and genetic damage (sulfidic nickel). When animal-based lung cancer dose-response functions for these compounds are extrapolated to humans, taking into account interspecies differences in deposition and clearance, differences in particle size distributions, and human work activity patterns, the predicted risks at occupational exposures are remarkably similar to those observed in nickel-exposed workers. This provides support for using the animal-based dose-response functions to estimate occupational exposure limits, which are found to be comparable to those in current use.
Nickel: Human Health and Environmental Toxicology
International Journal of Environmental Research and Public Health
Nickel is a transition element extensively distributed in the environment, air, water, and soil. It may derive from natural sources and anthropogenic activity. Although nickel is ubiquitous in the environment, its functional role as a trace element for animals and human beings has not been yet recognized. Environmental pollution from nickel may be due to industry, the use of liquid and solid fuels, as well as municipal and industrial waste. Nickel contact can cause a variety of side effects on human health, such as allergy, cardiovascular and kidney diseases, lung fibrosis, lung and nasal cancer. Although the molecular mechanisms of nickel-induced toxicity are not yet clear, mitochondrial dysfunctions and oxidative stress are thought to have a primary and crucial role in the toxicity of this metal. Recently, researchers, trying to characterize the capability of nickel to induce cancer, have found out that epigenetic alterations induced by nickel exposure can perturb the genome. The ...
Concise Review of Nickel Human Health Toxicology and Ecotoxicology
Inorganics, 2019
Nickel (Ni) metal and Ni compounds are widely used in applications like stainless steel, alloys, and batteries. Nickel is a naturally occurring element in water, soil, air, and living organisms, and is essential to microorganisms and plants. Thus, human and environmental nickel exposures are ubiquitous. Production and use of nickel and its compounds can, however, result in additional exposures to humans and the environment. Notable human health toxicity effects identified from human and/or animal studies include respiratory cancer, non-cancer toxicity effects following inhalation, dermatitis, and reproductive effects. These effects have thresholds, with indirect genotoxic and epigenetic events underlying the threshold mode of action for nickel carcinogenicity. Differences in human toxicity potencies/potentials of different nickel chemical forms are correlated with the bioavailability of the Ni2+ ion at target sites. Likewise, Ni2+ has been demonstrated to be the toxic chemical speci...