Oxidative DNA damage in cultured cells and rat lungs by carcinogenic nickel compounds (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, its adverse health effects & oxidative stress
Nickel-induced toxicity and carcinogenicity, with an emphasis on the generation and role of reactive oxygen species is reviewed. Nickel is a known haematotoxic, immunotoxic, neurotoxic, genotoxic, reproductive toxic, pulmonary toxic, nephrotoxic , hepatotoxic and carcinogenic agent. This article presents a selective review on nickel and effect of its acute, subchronic and chronic doses on certain metabolically active tissues in human as well as animals. Nickel exposure causes formation of free radicals in various tissues in both human and animals which lead to various modifications to DNA bases, enhanced lipid peroxidation, and altered calcium and sulphhydryl homeostasis. The primary route for nickel toxicity is depletion of glutathione and bonding to sulphhydryl groups of proteins. Nickel homeostasis, nickel-induced activation of signaling pathways and the protective role of enzymatic and non-enzymatic antioxidants against nickel toxicity and carcinogenicity are also discussed.
Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2005
The effects of nickel sulfate, and soluble forms of nickel carbonate hydroxide (NiCH), nickel subsulfide, and nickel oxide on delayed induction of DNA single-strand breaks (DNA SSBs) in chromosomal and nuclear chromatin of human blood lymphocytes in culture were studied. After 46 h of initial culture in supplemented RPMI-1640 media at 37 • C, human whole blood lymphocytes in culture were exposed to low concentrations (0-15 M) of different nickel (Ni) compounds for 2 h, whereas only RPMI-1640 medium served as control. Immediately after 2 h of such exposure, both control and Ni-treated cells were washed with the same medium and incubated further in fresh complete RPMI-1640 culture medium for another 24 h. After a total 70 h of incubation, cells were then arrested at metaphase. Two hours later, the induction of DNA SSBs involving both metaphase chromosomal and interphase nuclear chromatin was measured using the method of electron microscopy in situ end-labeling. The metaphase chromosomal chromatin showed significantly higher DNA SSBs (as measured by an increase in immunogold particles per m 2 chromatin) due to 15 M NiCH and NiO when compared to the corresponding control value. Both NiCH and nickel oxide produced significantly higher induction of DNA SSBs than those of nickel subsulfide and nickel sulfate in chromosomal chromatin. The DNA SSBs in chromosomal chromatin were found to be significantly higher than those in nuclear chromatin due to different Ni compounds. Overall, the genotoxic potency seems to be decreased as follows: NiCH > nickel oxide ≥ nickel subsulfide > nickel sulfate. Pretreatment of human blood lymphocytes with either catalase (a H 2 O 2 scavenger), or superoxide dismutase (a scavenger of O 2 − radical) or dimethylthiourea (a hydroxyl radical scavenger), or N-acetylcysteine (GSH precursor) significantly reduced DNA SSBs in both chromosomal and nuclear chromatin induced by NiCH, suggesting the involvement of different types of oxidative stress in such genotoxicity. Deferoxamine (a highly specific iron chelator) pretreatment prevented NiCH-induced DNA SSBs in both chromosomal and nuclear chromatin suggesting a role of iron-mediated oxidative stress generating hydroxyl radical in such genotoxicity. Simultaneous treatment with either verapamil (an inhibitor of Ca 2+ through * Corresponding author. Bemba-Meka et al. / Mutation Research 586 (2005) 124-137 125 plasma membranes), or dantrolene (an inhibitor of mobilization of [Ca 2+ ] i from endoplasmic reticulum), or BAPTA (a Ca 2+ chelator) significantly reduced Ni compound-induced DNA SSBs in both chromosomal and nuclear chromatin, suggesting that Ni compound-induced destabilization of calcium homeostasis may also involved in the induction of such DNA SSBs.
Primary concept of nickel toxicity - an overview
Journal of basic and clinical physiology and pharmacology, 2018
Toxic metals, including excessive levels of essential metals tend to change biological structures and systems into either reversible or irreversible conformations, leading to the derangement of organ functions or ultimate death. Nickel, a known heavy metal is found at very low levels in the environment. Nickel is available in all soil types and meteorites and also erupts from volcanic emissions. In the environment, nickel is principally bound with oxygen or sulfur and forms oxides or sulfides in earth crust. The vast industrial use of nickel during its production, recycling and disposal has led to widespread environmental pollution. Nickel is discharged into the atmosphere either by nickel mining or by various industrial processes, such as power plants or incinerators, rubber and plastic industries, nickel-cadmium battery industries and electroplating industries. The extensive use of nickel in various industries or its occupational exposure is definitely a matter of serious impact on human health. Heavy metals like nickel can produce free radicals from diatomic molecule through the double step process and generate superoxide anion. Further, these superoxide anions come together with protons and facilitate dismutation to form hydrogen peroxide, which is the most important reason behind the nickel-induced pathophysiological changes in living systems. In this review, we address the acute, subchronic and chronic nickel toxicities in both human and experimental animals. We have also discussed nickel-induced genotoxicity, carcinogenicity, immunotoxicity and toxicity in various other metabolically active tissues. This review specifically highlighted nickel-induced oxidative stress and possible cell signaling mechanisms as well.
Carcinogenesis, 2002
Nickel compounds are well-known human carcinogens, but the underlying mechanisms are still not fully understood. Even though only weakly mutagenic, nickel chloride has been shown previously to impair the repair of UV-induced DNA damage as well as oxidative DNA damage. However, the carcinogenic potential depends largely on solubility, with poorly water-soluble nickel subsulfide and nickel oxide being strong carcinogens. Within the present study we investigated the effects of particulate black NiO and soluble NiCl 2 on the induction and removal of stable DNA adducts formed by benzo[a]pyrene (B[a]P) measured by a highly sensitive high performance liquid chromatography (HPLC)/fluorescence assay. With respect to adduct formation, NiO but not NiCl 2 reduced the generation of DNA lesions by~30%. Regarding their repair, in the absence of nickel compounds, most lesions were removed within 24 h; nevertheless, between 20 and 35% of induced adducts remained even 48 h after treatment. NiCl 2 and NiO reduced the removal of adducts in a dose-dependent manner. Thus, 100 µM NiCl 2 led to~80% residual repair capacity; after 500 µM the repair was reduced to~36%. Also, even at the completely non-cytotoxic concentration of 0.5 µg/cm 2 black NiO, lesion removal was reduced to~35% of control and to 15% at 2.0 µg/cm 2 . Furthermore, both nickel compounds increased the benzo[a]pyrene-7,8-diol 9,10epoxide (BPDE)-induced cytotoxicity. Taken together, our results indicate that the nucleotide excision repair pathway is affected in general by water-soluble and particulate nickel compounds and provide further evidence that DNA repair inhibition may be one predominant mechanism in nickel-induced carcinogenicity.
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.
Genotoxic effects of two nickel-compounds in somatic cells of Drosophila melanogaster
Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2011
In view of the scarcely available information on the in vivo mutagenic and co-mutagenic activity of nickel, the genotoxic potential of two nickel-compounds, nickel chloride (NiCl 2 ) and nickel sulphate (NiSO 4 ), was assessed in Drosophila melanogaster by measuring two different genetic endpoints. On the one hand, we used the wing-spot assay, which is based on the principle that the loss of heterozygosity of two suitable recessive markers, multiple wing hairs (mwh) and flare-3 (flr 3 ), can lead to the formation of mutant clones in the imaginal disks of larval cells. On the other hand, the in vivo comet assay, which detects single-and double-strand DNA breaks, was also used with larval haemocytes. These cells offer several advantages: they are highly sensitive to genotoxic agents, the sampling and processing methodologies are quite simple and the level of basal DNA damage is relatively low. No significant increases in the frequencies of the three categories of mutant spots (i.e. small single spots, large single spots, and twin spots) were observed in the wing-spot assay; however, NiSO 4 induced significant dose-dependent increases in DNA damage in the comet assay. In addition, the combined treatments with gamma-radiation and NiCl 2 and NiSO 4 showed a slight but significant increase in the frequency of the three categories of mutant spots compared with the frequency induced by gamma-radiation alone, indicating that both nickel compounds have a synergistic interaction. These results support the assumption that both nickel compounds could act as co-mutagens interfering with DNA-repair processes and that the in vivo comet assay is a sensitive and effective method for detecting the DNA damage induced by NiSO 4 in haemocytes of D. melanogaster.
Nickel (II)-induced apoptosis and G2/M enrichment
Experimental & Molecular Medicine, 1998
Treatment with certain DNA-damaging agents induce a complex cellular response comprising pertubation of cell cycle progression and/or apoptosis on proliferating mammalian cells. Our studies were focused on the cellular effects of nickel (II) acetate, DNAdamaging agent, on Chinese hamster ovary (CHO) cells. Fragmented DNAs were examined by agarose gel electrophoresis and cell cycle was determined by DNA flow cytometry using propidium iodide fluorescence. Apparent DNA laddering was observed in cells treated with 240 M nickel (II) and increased with a concentration-dependent manner. Tr e a t m e n t of nickel (II) acetate resulted in apoptosis which was accompanied by G 2 /M cell accumulation. Proportion of CHO cells in G 2 /M phase was also significantly increased in cells exposed to at least 480 M nickel (II) from 57.7% of cells in the G 0 / G 1 phase, 34.7% in the S phase, and 7.6 % in the G 2 /M phase for 0 M nickel (II), to 58.6%, 14.5%, and 26.9% for 640 M nickel (II). These findings suggest that nickel (II) can modulate cellular response through some common effectors involving in both apoptotic and cell cycle regulatory pathways.
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...