Toxicological interactions between nickel and radiation on chromosome damage and repair.

Abstract

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.-Environ Health Perspect 102(Suppl 9): 73-77 (1994)

Nickel subsulfide is similar to potassium dichromate in protecting normal human fibroblasts from the mutagenic effects of benzo[a]pyrene diolepoxide

“…One possibility previously suggested is that nickel inhibits DNA repair and, thus, inhibits the ability of the cell to eliminate DNA damage. This hypothesis has been supported by reports that nickel can inhibit several DNA repair processes [Hartwig and Beyersmann, 1989a,b;Snyder et al, 1989;Au et al, 1994;Porter et al, 1997;Lee-Chen et al, 1993]. Our antagonistic results are contrary to this hypothesis, however, since a protective effect, such as the one shown above, would result from a stimulation of DNA repair instead of inhibition.…”

“…These data show that soluble nickel sulfate can also produce an antagonistic effect and support the hypothesis that the difference between our results and the previous studies may be due to a species difference. It should be noted, however, that Au et al [1994] reported a synergistic effect of nickel and ␥-rays on chromosome translocations in human lymphocytes, suggesting the differences in results may be more complicated than a simple species difference.…”

Evaluation of Nickel–Zinc Interactions by Means of Bioassays with Amphibian Embryos

“…On the other hand, Ni can bind to DNA and proteins in cells in vitro and to chromatin in vivo. Such binding to macromolecules could be correlated to the ability of Ni compounds to interfere with DNA synthesis and to induce slight increases in chromosome alterations, as well as its mutagenic action (Morita et al, 1991;Au et al, 1994;Sarkar, 1995). It has also been suggested that Ni-induced abnormal DNA repair may be a mechanism for carcinogenesis (Au et al, 1994;Hartmann and Hartwig, 1998).…”

Contribution to the validation of the anaphase-telophase test: aneugenic and clastogenic effects of cadmium sulfate, potassium dichromate and nickel chloride in Chinese hamster ovary cells

“…Our results showed that Ni (II) had little or no clastogenic activity under the experimental conditions employed. According to Au et al (1994), nickel compounds are weakly mutagenic and may therefore be carcinogenic because of non-conventional genotoxic mechanisms including aneuploidy. On the other hand, the concentrations employed in these experiments may have been too low to induce DNA breakage.…”

“…Hartwig and Beyersmann (1989) showed that nickel chloride was cytotoxic and mutagenic in V79 cells treated with concentrations of 0.5-2 mM for 5 h. Littlefield et al (1994) reported that this salt (100 µM/l for 16 h) induced DNA strand breaks in a human B-lymphoblastoid cell line and in rat primary splenocytes. Au et al (1994) found no increase in SCE and chromosomal aberrations in lymphocytes exposed to 0.1-100 µM for 1 h. Patierno et al (1993) reported that nickel sulfate was cytotoxic to rat epithelial cells at doses of 50-200 µg/ml and induced transformation in these cells.…”