Modification of 7,8-benzoflavone metabolism in hamster liver and kidney microsomes by hepatic tumor inducing treatments

Abstract

The effect of pre-treatment of male Syrian golden hamsters with 7,8-benzoflavone (BF), with diethylstilbestrol (DES) and with BF plus DES on the metabolism of [14C]BF in hepatic and renal microsomes has been studied in vitro. Whereas hepatic microsomes from DES-treated animals produced the same pattern of BF metabolites as control microsomes, a marked quantitative and qualitative alteration of BF metabolism was observed with liver microsomes from animals pre-treated with BF and with BF plus DES: the metabolic rate was increased and three new metabolites were formed which were not observed with control hepatic microsomes. These metabolites, which were tentatively identified as BF-5,6-dihydrodiol and two isomeric dihydroxy-BFs, were not detected in incubations with renal microsomes under any pre-treatment regimen. Non-extractable binding of radioactivity to hepatic and renal microsomal protein was observed in all incubations but did not exhibit as pronounced a dependence on pre-treatment as did the pattern of BF metabolites. Based on the metabolic data it is concluded that BF induces its own oxidative metabolism. Among the metabolites are reactive intermediates that bind to cellular macromolecules and may play an important role in tumor formation in the male Syrian hamster liver following prolonged treatment with BF plus DES.