TOXICOLOGICAL INTERACTIONS BETWEEN NICKEL AND RADIATION ON CHROMOSOME-DAMAGE AND REPAIR

Carcinogenic nickel compounds are usually found to be weak mutagens; t herefore these compounds may not exert their carcinogenic activity thr ough conventional genotoxic mechanisms. On the other hand, the activit ies of many nickel compounds have not been adequately investigated. We evaluated the genotoxic activities of nickel acetate using convention al chromosome aberration and sister chromatid exchange assays and foun d that there was no increase of chromosome aberrations or sister chrom atid exchanges, although the highest dose (1000 mu M) caused mitotic i nhibition. In addition, we investigated its effect on DNA repair using our challenge assay. In this assay, lymphocytes were exposed to 0.1 t o 100 mu M nickel acetate for 1 hr during the G0 phase of the cell cyc le. The cells were washed free of the chemical and, 1.5 hr later, were irradiated with two doses of gamma-rays (75 cGy per dose separated by 60 min). A significant dose-dependent increase of chromosome transloc ations was observed (p<0.05). The increase is more than expected based on additive effects from exposure to nickel or gamma-rays individuall y. 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 pretrea tment with nickel interferes with the repair of radiation-induced DNA damage and potentially cause mistakes in DNA repair. Furthermore, we s uggest 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 adapt ive response. Contrary to some investigators who showed that adaptive responses may he beneficial, our data indicated that some responses ma y cause more problems than expected.