| 6838636 |
Iba MM, Sikka HC: Induction of hepatic microsomal cytochrome P-448-mediated oxidases by 3,3'-dichlorobenzidine in the rat. Biochem Pharmacol. 1983 Mar 1;32(5):901-9.
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. |
1(0,0,0,1) |