Differential induction of sister-chromatid exchanges by benzo[a]pyrene in variant mouse hepatoma cells

Two variant mouse hepatoma cell lines had been separated from a parent cell line, Hepa-1c1c7, by fluorescence activated cell sorting. Earlier metabolic studies had shown that variant TAOc1BPrc1 was more active in the metabolism of the indirect carcinogen benzo[a]pyrene than was variant BPrc1. In an extension of these studies, the relationship between the metabolic capabilities of these two cell lines and the induction of sister-chromatid exchanges by B[a]P was investigated. It was observed that TAOc1BPrc1 yielded a significant dose-dependent increase in the induction of SCE by B[a]P whereas BPrc1 did not show a response significantly greater than control. Metabolic results indicated that the induction of SCE in TAOc1BPrc1 was due to the production of 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene by this variant. This metabolite did not appear to be produced by BPrc1. Furthermore, TAOc1BPrc1 required only 40 nM B[a]P to induce a 2-fold increase in SCE frequency. This concentration is considerably lower than that required to elicit a similar response in other reported cell lines. To our knowledge, this is the first report of the use of a mouse hepatoma cell line for determining the relationship of metabolic capability to the induction of SCE.