Metabolism of 2-acetylaminofluorene by eight different forms of cytochrome P-450 isolated from rat liver

Abstract

Eight different forms of cytochrome P-450 were isolated from the liver microsomes of male Sprague-Dawley rats and compared with previously characterized forms on the basis of chromatographic behavior, absorption maximum of the carbon monooxide complex, apparent MW upon SDS[sodium dodecyl sulfate]-disc gel electrophoresis and substrate specificity. With respect to 2-acetylaminofluorene [a potent hepatocarcinogen in the male rat] metabolism in a reconstituted system involving these cytochromes P-450, form c was .apprx. 16 times as active as form d, which was in turn at least 30 times as active as any of the other forms. The patterns of metabolites obtained with all of the cytochromes P-450 were determined by high-performance liquid chromatography and were all unique. Form d was as active as form c in producing N-hydroxy-2-acetylaminofluorene. This metabolite was observd with only 1 other form of the cytochrome, i.e., form PB/PCN-E, which gave rise to it at a very low rate.