Cytotoxic and mutagenic effects of anti- and syn-benzo[a]pyrene diol epoxide in human lymphocytes

Cytotoxicity and mutagenicity were measured in human lymphocytes after treatment in vitro with anti- or syn-benzo[a]pyrene diolepoxide, two diastereoisomer metabolites of benzo[a]pyrene. These compounds were incubated with resting and cycling lymphocytes to determine the inhibition of cell proliferation induced by phytohemoagglutinin and interleukin2 at different times after treatment. Anti-benzo[a]pyrene diolepoxide was more cytotoxic than the syn-adduct under all conditions, and its effect on cell growth was more marked in cycling lymphocytes. In contrast, neither of the compounds induced alteration of the ATP intracellular pool. Cytotoxic effects of anti- and syn-benzo[a]pyrene diolepoxide were also assessed by determining the cloning efficiency. Both compounds affected the cloning efficiency in human lymphocytes and the effect of anti-benzo[a]pyrene was particularly marked. Mutagenic potency of anti- and syn-benzo[a]pyrene diolepoxide at the hgprt locus was measured both in the V79 cell line and in human lymphocytes by selection of mutant cells in medium containing 6-thioguanine. Both compounds increased the mutant frequency in comparison with the control and anti-benzo[a]pyrene diolepoxide was more active than the syn-metabolite.