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 extensively studied, even though the effect of individual carcinogens is, in many cases, well known. We have previously shown that potassium dichromate can protect normal human fibroblasts from the mutagenic effects of benzo[a]pyrene diolepoxide (BPDE), and that this effect may be via an oxidative stress mechanism [Tesfai et al. (1998) Mutat Res 416:159-168]. Here, we extend our previous work by showing that nickel subsulfide can produce the some effect. 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)phosphoribosyl-transferase (HPRT) gene when compared to cells treated only with BPDE. The preincubation period with nickel subsulfide was necessary to see the antagonistic effect, since it was not observed if the cells were simply incubated with both carcinogens for 2 hr. The extent of the antagonistic effect was nickel subsulfide dose-dependent and also appeared to be species-specific, since the effect was not observed when Chinese hamster fibroblasts 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-specific, and that it could be species-specific.
Hamdan
S
S
Department of Chemistry, Western Michigan University, Kalamazoo, USA.
Morse
B
B
Reinhold
D
D
D000818:Animals; D001580:Benzopyrenes / Q000633:toxicity*; D002460:Cell Line; D002999:Clone Cells / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004252:DNA Mutational Analysis; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D016296:Mutagenesis / Q000187:drug effects*; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation / Q000187:drug effects; D009532:Nickel / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011192:Potassium Dichromate / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013045:Species Specificity; D013997:Time Factors; D014810:Vitamin E / Q000494:pharmacology
D001580:Benzopyrenes; D009153:Mutagens; D017382:Reactive Oxygen Species; D014810:Vitamin E; C072019:benzo(a)pyrene diolepoxide I; D009532:Nickel; D007041:Hypoxanthine Phosphoribosyltransferase; D011192:Potassium Dichromate; C017557:nickel subsulfide