PT  - JOURNAL ARTICLE
AU  - CECILIA SCHELIN
AU  - ANDERS TUNEK
AU  - BENGT JERNSTROM
AU  - BENGT JERGIL
TI  - Irreversible Binding of Isolated Benzo[<em>a</em>]pyrene Metabolites to Specific Rat Liver Microsomal Proteins
DP  - 1980 Nov 01
TA  - Molecular Pharmacology
PG  - 529--535
VI  - 18
IP  - 3
4099  - http://molpharm.aspetjournals.org/content/18/3/529.short
4100  - http://molpharm.aspetjournals.org/content/18/3/529.full
SO  - Mol Pharmacol1980 Nov 01; 18
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.