Induction of hepatic microsomal cytochrome P-448-mediated oxidases by 3,3'-dichlorobenzidine in the rat.
Intraperitoneal administration of the hepatocarcinogen 3,3'-dichlorobenzidine (4,4'-diamino, 3,3'-dichlorobiphenyl) to adult male rats caused the induction of hepatic microsomal ethoxycoumarin O-deethylase and p-nitrophenetole O-deethylase activities comparable in magnitudes to those induced by 3-methylcholanthrene; neither aniline hydroxylase nor aminopyrine N-demethylase activity was affected by the pretreatment. The induction was not accompanied by a significant increase in content of hepatic microsomal cytochrome P-450; however, a shift in the absorption maximum of the reduced + CO spectrum of the cytochrome to 448 nm and an increase in the ratio of the 455 nm:430 nm peaks of the reduced + ethylisocyanide spectrum of the hemoprotein was effected. Arylhydrocarbon hydroxylase activity was stimulated 5-fold by dichlorobenzidine pretreatment in comparison with a 12-fold stimulation following 3-methylcholanthrene pretreatment. However, enzymically mediated covalent binding of benzo[a]pyrene to microsomal protein was greater in microsomes from dichlorobenzidine-pretreated rats than in those from methylcholanthrene-pretreated rats. All of the dichlorobenzidine-induced enzymic activities were inhibited by alpha-naphthoflavone but not by SKF-525A. Hepatic microsomes from dichlorobenzidine-pretreated rats appeared to have a higher capacity for metabolizing dichlorobenzidine than those from untreated animals; both sets of microsomes elicited the Type II spectral change on combination with the compound, albeit with different binding affinities and capacities. The results show that dichlorobenzidine, although only a dihalogenated biphenyl derivative, is a potent inducer of cytochrome P-448.
D015101:3,3'-Dichlorobenzidine / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001560:Benzidines / Q000494:pharmacology*; D019388:Cytochrome P-450 CYP1A2; D003580:Cytochromes / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology*; D010088:Oxidoreductases / Q000096:biosynthesis*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D001560:Benzidines; D003580:Cytochromes; D015101:3,3'-Dichlorobenzidine; D008748:Methylcholanthrene; D010088:Oxidoreductases; D001189:Aryl Hydrocarbon Hydroxylases; C017170:Cyp1a2 protein, rat; D019388:Cytochrome P-450 CYP1A2; D010634:Phenobarbital