CYTOTOXIC AND MUTAGENIC EFFECTS OF ANTI-BENZO[A]PYRENE 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 in cubated with resting and cycling lymphocytes to determine the inhibiti on of cell proliferation induced by phytohemoagglutinin and interleuki n2 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 contr ast, neither of the compounds induced alteration of the ATP intracellu lar pool. Cytotoxic effects of anti- and syn-benzo[a]pyrene diolepoxid e were also assessed by determining the cloning efficiency. Both compo unds affected the cloning efficiency in human lymphocytes and the effe ct of anti-benzo[a]pyrene was particularly marked. Mutagenic potency o f anti- and syn-benzo[a]pyrene diolepoxide at the hgprt locus was meas ured both in the V79 cell line and in human lymphocytes by selection o f mutant cells in medium containing 6-thioguanine. Both compounds incr eased the mutant frequency in comparison with the control and anti-ben zo[a]pyrene diolepoxide was more active than the syn-metabolite.