Toxicological interactions between nickel and radiation on chromosome damage and repair.
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 microM) 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 microM nickel acetate for 1 hr during the G0 phase of the cell cycle. 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 translocations was observed (p < 0.05). The increase is more than expected based on additive effects from exposure to nickel or gamma-rays 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.(ABSTRACT TRUNCATED AT 250 WORDS)
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Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston 77555-1010.
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D000085:Acetates / Q000494:pharmacology*; D019342:Acetic Acid; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000528:radiation effects*; D008297:Male; D012854:Sister Chromatid Exchange
D000085:Acetates; D019342:Acetic Acid