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

The cellular response to multiple carcinogen treatment has not been extensi vely studied, even though the effect of individual carcinogens is, in many cases, well known. We have previously shown that potassium dichromate can p rotect normal human fibroblasts From the mutagenic effects of benzo[a]pyren e diolepoxide (BPDE), and that this effect may be via an oxidative stress m echanism [Tesfai et at. (1998) Mutat Res 416: 159-168]. Here, we extend our previous work by showing that nickel subsulfide con produce the same effec t. Normal human fibroblasts, preincubated with nickel subsulfide for 46 hr followed by a coincubation of nickel subsulfide and BPDE for 2 hr, showed a dramatic reduction in the mutant frequency of the hypoxanthine (guanine)ph osphoribosyl-transferase (HPRT) gene when compared to cells treated only wi th BPDE. The preincubation period with nickel subsulfide was necessary to s ee the antagonistic effect, since ii was not observed if the cells were sim ply incubated with both carcinogens for 2 hr. The extent of the antagonisti c effect was nickel subsulfide dose-dependent and also appeared to be speci es-specific, since the effect was not observed when Chinese hamster fibrobl asts were tested. Finally, the antagonistic effect of the nickel subsulfide was eliminated by vitamin E, suggesting that production of reactive oxygen species by the nickel may be required. This data, along with our previous work, suggest that the antagonistic effect we observe is not chromium-speci fic, and that it could be species-specific. (C) 1999 Wiley-Liss, Inc.