Comparative effect of phenobarbital and 3-methyl-cholanthrene on azodye metabolism in rat liver. I. In vitro studies on detoxication and activation processes.

The effect of phenobarbital (PB) and 3-methylcholanthrene (3-MC) administration on detoxication and activation of the carcinogenic azodye 4-dimethyl-aminoazobenzene (DAB) was studies in rat liver microsomes. Azoreductase activity and in vitro DAB metabolite binding to calf thymus DNA and microsomal protein were simultaneously determined. Pretreatment of rats with 3 daily injections of PB (80 mg/kg) did not significantly modify azoreductase activity by increased DAB metabolite binding to DNA (+ 67%) and to protein (+ 123%). The effect of 3-MC differed according to the route of administration. When it was given intraperitoneally (1 times 20 mg/kg)azoreductase was not modified and DAB metabolite binding to DNA and to protein was eight-fold enhance. After continuous administration of 3-MC in the diet (3.0 MG/KG/DAY)AZOREDUCTASE ACTIVITY WAS DECREASED (MINUS 40%), DAB metabolite binding to DNA was unchanged and DAB metabolite binding to protein tripled. Thus the balance between the formation of DAB metabolites bound to DNA and azoreduction led to an increased activation/reduction ratio only by 3-MC injection. In every case, the formation of DAB metabolites bound to protein was significantly increased as compared with detoxication. Different effects of PB and 3-MC were discussed with reference to the synthesis of distinct cytochromes.