Lack of induction of sister chromatid exchanges and of mutation to 6-thioguanine resistance in V79 cells by butylated hydroxyanisole with and without activation by rat or hamster hepatocytes.
The antioxidant butylated hydroxyanisole (BHA) and the promutagen/carcinogen 7,12-dimethylbenz[a] anthracene (DMBA) were examined for mutagenicity and the induction of sister chromatid exchanges (SCE) in a hepatocyte-mediated mutation assay with V79 Chinese hamster lung cells. Rat and hamster hepatocytes, prepared by in situ collagenase perfusion, were compared in the mutation assay to determine whether there are species differences in the ability to activate BHA and DMBA to ultimate mutagens. At the marginally cytotoxic concentration of 1.0 microM (2.6 micrograms/ml), DMBA induced a significant increase in the frequency of SCE and in the number of mutations to 6-thioguanine resistance (6-TGR) at the hypoxanthine-guanine phosphoribosyltransferase (HGPRT) locus with either rat or hamster hepatocyte-mediated activation, but induced highest mutation frequencies with rat hepatocytes. These findings support the contention that species differences can affect mutational response in hepatocyte-mediated assays with V79 cells. BHA was strongly cytotoxic to V79 cells at dose levels in excess of 0.3 mM (54 micrograms/ml). In contrast to DMBA, BHA showed no evidence of genotoxicity at marginally cytotoxic concentrations up to and including 0.3 mM as shown by the inability of this antioxidant to increase the frequency of sister chromatid exchanges or to induce mutations to 6-thioguanine resistance when activation was provided by rat or hamster hepatocytes.
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000840:Anisoles / Q000633:toxicity*; D001711:Biotransformation; D002083:Butylated Hydroxyanisole / Q000378:metabolism / Q000633:toxicity*; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004351:Drug Resistance; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D008647:Mesocricetus; D009154:Mutation; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013866:Thioguanine / Q000494:pharmacology*
D000840:Anisoles; D002083:Butylated Hydroxyanisole; D015127:9,10-Dimethyl-1,2-benzanthracene; D013866:Thioguanine