Nickel potentiates the genotoxic effect of benzo[a]pyrene in Chinese hamster lung V79 cells

The modulating effect of acute exposure to NiCl₂ on the induction of chromosome aberrations by a model carcinogen, benzo[a]pyrene (B[a]P), was examined in Chinese hamster V79 lung cells. At concentrations up to 20 μg/ml (84.2 μM), NiCl₂ did not significantly increase the frequency of chromosome aberrations in V79 cells when the cells were exposed concomitantly to 0.5 μg/ml B[a]P. Addition of the S15 liver microsomal fraction together with the B[a]P did not alter the results. Addition of NiCl₂ 2 hr before treatment of cells with 0.5 μg/ml B[o]P also did not result in a significant elevation of the frequency of chromosome aberrations, even at NiCl₂ concentrations as high as 20 μg/ml. Contrasting sharply with these findings, when V79 cells were treated with NiCl₂ immediately after B[a]P exposure, a significant increase in the frequency of chromosome damage was observed at NiCl₂ concentrations as low as 5 μg/ml (21.1 μM). NiCl₂-mediated enhancement of chromosome damage was also observed when V79 cells were exposed to the reactive B[a]P intermediate, benzo[a]pyrene-r-7,t-8-dihydrodiol-t-9,10-epoxide (BPDE). In the BPDE-treated cells, the level of NiCl₂-mediated enhancement was similar to that observed with the tumor promoter 12-o-tetradecanoylphorbol-13- acetate (TPA, 100 ng/ml). These results are consistent with the view that the effect of nickel (II) on B[a]P-induced genetic damage is dependent on the relative times of exposure to Ni²⁺ and B[a]P. NiCl₂ did not enhance the frequency of chromosome aberrations induced by Chromium (VI), regardless of the order of addition of the chemicals to the V79 cells. These results suggest that nickel may act as a promoter of chemically-induced genetic damage through induction of error-prone repair.