Comparative effect of phenobarbital and 3-methylcholanthrene on azo dye metabolism in rat liver. II. In vivo binding of metabolites to cellular macromolecules.

The binding of 4-dimethylaminoazobenzene (DAB) metabolites to liver total protein and nuclear DNA was studied in rats pretreated with phenobarbital (PB) or 3-methylcholanthrene (3-MC), then fed with a (-14C)DAB diet (0.06%) for 3 days. Three consecutive injections of PB (80mg-kg) led to a 50% decrease of DAB metabolites bound to total protein and nuclear DNA. A single injection of 3-MC(20 mg-kg) roughly doubled the amount of metabolites bound to nuclear DNA but did not modify those bound to protein. When given in the diet (0.005%) for 8 days before the (-14C)-DAB diet, 3-MC did not change the amount of DAB metabolites bound either to protein, or to DNA. The opposite effect of PB and 3-MC injections on azodye binding to cellular constituents might be relevant to the action of these drugs on carcinogenesis. Moreover the route of 3-MC administration might be meaningful since DAB metabolite binding to DNA was only increased by intraperitoneal injection.