RT Journal Article SR Electronic T1 Irreversible Binding of Isolated Benzo[a]pyrene Metabolites to Specific Rat Liver Microsomal Proteins JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 529 OP 535 VO 18 IS 3 A1 CECILIA SCHELIN A1 ANDERS TUNEK A1 BENGT JERNSTROM A1 BENGT JERGIL YR 1980 UL http://molpharm.aspetjournals.org/content/18/3/529.abstract AB [3H]Benzo[a]pyrene and seven isolated [3H]benzo[a]pyrene metabolites were incubated with liver microsomes from control, phenobarbital-, and 3-methylcholanthrene-treated rats, and irreversible binding to microsomal proteins was studied. For all compounds tested, including benzo[a]pyrene-4,5-oxide, the binding was greatly enhanced in the presence of a NADPH-generating system. All metabolites except 3-hydroxybenzo[a]-pyrene bound more extensively to microsomal proteins from 3-methyicholanthrene-treated rats than to proteins from phenobarbital-treated or control rats. Benzo[a]pyrene-7,8-dihydrodiol bound much more efficiently than the other metabolites. The protein binding patterns of the metabolites were examined by SDS-polyacrylamide gel electro-phoresis and fluorography. The most extensive binding occurred to a few proteins in the MW region of 45,000-70,000, and there were differences in the patterns between different metabolites. The composite pattern of the metabolites corresponded to the binding pattern obtained with benzo[a]pyrene. A major target protein in microsomes from 3-methylcholanthrene-treated rats had the same mobility as purified cytochrome P-448. Most binding to microsomes from phenobarbital-treated animals occurred to a 60,000 MW component. Binding also occurred to a protein which comigrated with cytochrome P-450. The specificity and extent of metabolite binding to proteins may be of importance for the development of cytotoxicity. Factors affecting the binding patterns are discussed.