Interindividual variation in benzo(a)pyrene metabolism and composition of isoenzymes of cytochrome P-450 as revealed by SDS-gel electrophoresis of human liver microsomal fractions.

Abstract

Human liver microsomal fractions from 13 different individuals were characterized with respect to SDS-polyacrylamide gel electrophoretic profiles and regiospecificity in the metabolism of the polyaromatic hydrocarbon benzo(a)pyrene. Pronounced interindividual differences in the composition of microsomal proteins in the molecular weight region of Mr=49,000-60,000 were found. Furthermore, gel electrophoresis combined with staining for peroxidase activity indicated most of the variations among the profiles of microsomal proteins being attributed to interindividual differences in the composition of isoenzymes of cytochrome P-450. One type of human liver microsomal fraction was selectively induced in specimens obtained from patients with known regular drug intake before death and correlated well in molecular weight to the phenobarbital-inducible form of cytochrome P-450 in the rabbit. Large variations among the human liver microsomal samples were also seen in the benzo(a)pyrene metabolism. The results indicate the presence of 7-8 different froms of cytochrome P-450 in human liver microsomes and that the interindividual variations seen in drug metabolism may at least in part be explained by interindividual variations in the distribution of these isoenzymes.