Gene (HPRT) and Chromosomal (MN) Mutations of Nickel Metal Powder in V79 Chinese Hamster cells (original) (raw)
Related papers
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.
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 ...
Toxicological interactions between nickel and radiation on chromosome damage and repair
Environmental Health Perspectives, 1994
Carcinogenic nickel compounds are usually found to be weak mutagens; therefore these compounds may not exert their carcinogenic activity through conventional genotoxic mechanisms. On the other hand, the activities of many nickel compounds have not been adequately investigated. We evaluated the genotoxic activities of nickel acetate using conventional chromosome aberration and sister chromatid exchange assays and found that there was no increase of chromosome aberrations or sister chromatid exchanges, although the highest dose (1000 pM) caused mitotic inhibition. In addition,. we investigated its effect on DNA repair using our challenge assay. In this assay, lymphocytes were exposed to 0.1 to 100 pM nickel acetate for 1 hr during the GO phase of the cell cycle. The cells were washed free of the chemical and, 1.5 hr later, were irradiated with two doses of y-rays (75 cGy per dose separated by 60 min). A significant dose-dependent increase of chromosome translocations was observed (p<0.05). The increase is more than expected based on additive effects from exposure to nickel or trays individually. In contrast to the increase of chromosome translocations, there was no increase in chromosome deletions, although there was a nickel dose-dependent reduction of mitotic indices. Our data suggest that pretreatment with nickel interferes with the repair of radiation-induced DNA damage and potentially cause mistakes in DNA repair. Furthermore, we suggest that nickel-induced abnormal DNA repair may be a mechanism for its carcinogenic properties. The DNA repair problems that we observed after exposure to low doses of nickel may be viewed as a type of adaptive response. Contrary to some investigators who showed that adaptive responses may be beneficial, our data indicated that some responses may cause more problems than expected.
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.
Heterochromatinization as a Potential Mechanism of Nickel-Induced Carcinogenesis
Biochemistry, 2009
Epigenetics refers to heritable patterns of gene expression that do not depend on alterations of the genomic DNA sequence. Nickel compounds have demonstrated carcinogenicity without any associated mutagenesis, suggesting that its mechanism of carcinogenesis is epigenetic in nature. One such potential mechanism is the heterochromatinization of chromatin within a region of the genome containing a gene sequence, inhibiting any further molecular interactions with that underlying gene sequence and effectively inactivating that gene. We report here the observation, by atomic force microscopy and circular dichroism spectropolarimetry, that nickel ion (Ni 2+) condenses chromatin to a greater extent than the natural divalent cation of the cell, magnesium ion (Mg 2+). In addition, we use a model experimental system that incorporates a transgene, the bacterial xanthine guanine phosphoribosyl transferase gene (gpt) differentially near to, and far away from, a heterochromatic region of the genome, in two cell lines, the Chinese hamster V79-derived G12 and G10 cells, respectively, to demonstrate by DNase I protection assay that nickel treatement protects the gpt gene sequence from DNase I exonuclease digestion in the G12 cells, but not in the G10 cells. We conclude that condensation of chromatin by nickel is a potential mechanism of nickel-mediated gene regulation.
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.
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.