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.
D000284:Administration, Oral; D000818:Animals; D002250:Carbon Radioisotopes; D004247:DNA / Q000378:metabolism; D003864:Depression, Chemical; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008748:Methylcholanthrene / Q000008:administration & dosage / Q000494:pharmacology*; D010634:Phenobarbital / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D013268:Stimulation, Chemical; D004124:p-Dimethylaminoazobenzene / Q000378:metabolism*
D002250:Carbon Radioisotopes; D011506:Proteins; D008748:Methylcholanthrene; D004247:DNA; D004124:p-Dimethylaminoazobenzene; D010634:Phenobarbital