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[Correlation between cytochrome P-448 content and benzopyrene hydroxylase activity during the induction of microsomal monooxygenases using methylcholanthrene-type xenobiotics].

Using antibodies against electrophoretically homogeneous cytochrome P-448 from rat liver microsomes induced by 3-methylcholanthrene, the changes in the immunologic identity and contents by cytochrome P-448 induced by 3-methylcholanthrene, 3.4-benzpyrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), were studied. No cytochrome P-448 was detected in the liver microsomes of control or phenobarbital-induced rats. This form of the cytochrome makes up to about 35% of the total content of the CO-binding hemoprotein during TCDD induction and up to 90% during 3-methylcholanthrene and 3,4-benzpyrene induction. On the other hand, 3-methylcholanthrene, 3,4-benzpyrene and TCDD significantly and equally activates the cytochrome P-448-dependent benzpyrene hydroxylase, since the antibodies against cytochrome P-448 inhibit benzpyrene metabolism in the microsomes by 85-90%. The possible reasons for the TCDD-induced increase in the catalytic activity of cytochrome P-448 as compared to the immunologically identical cytochrome P-448 induced by 3-methylcholanthrene and 3,4-benzpyrene, are discussed.

Animals↗

Characterization of benzopyrene metabolism in rat pancreas.

The present studies characterized the pancreatic metabolic system which biodegrades benzo[a]pyrene (BP), in male Sprague-Dawley rats pretreated with 20 mg/kg 3-methylcholanthrene (3MC), 75 mg/kg phenobarbital (PB) or solvent as control. Type of cytochrome involved was examined by measuring the reaction in the presence of 7,8-benzoflavone (BF), an inhibitor of the cytochrome P-448-related enzyme activity. The data indicated that the enzyme activity was induced by pretreatment with PB but not with 3MC. These pretreatment protocols resulted in changes both in Km and Vmax. Studies with BF suggested that pancreatic tissue may not contain more than one class of hemoprotein. These studies pointed out species differences between the rat and guinea pig, and confirmed the pancreatic capability to metabolize procarcinogens and to further degrade carcinogenic metabolites.

9,10-Dimethyl-1,2-benzanthracene↗