The contribution of specific cytochromes P-450 in the metabolism of 7,12-dimethylbenz[a]anthracene in rat and human liver microsomal membranes

Chemico-biological Interactions
V M MorrisonJ A Craft

Abstract

The role of specific cytochrome P-450 isoenzymes in the regio-selective metabolism of 7,12-dimethylbenz[a]anthracene (DMBA) has been studied in microsomal membranes from rat and human liver. An antibody inhibition study using membranes from phenobarbital-treated rats demonstrates that a member(s) of the CYP2C family accounts for up to 90% of the formation of the proximate carcinogen, DMBA-3,4-diol, and makes significant contributions to the formation of DMBA-5,6-diol and DMBA-8,9-diol. In these membranes the formation of DMBA-5,6-diol can be entirely accounted by the combined activity of members of the CYP2C and CYP2B families. The metabolism of DMBA has been investigated in human using microsomes from 10 individuals and the metabolites formed by these membranes were found to be mainly hydroxymethyl- and -diol products. The rates of formation of each metabolite show considerable interindividual variation and there was no correlation between these rates for any pairing of metabolites. The CYP content in these membranes of specific members of families 1, 2, 3 and 4 did correlate with the rates of formation of individual metabolites. Surprisingly there was no correlation between the content of CYP2C and formation of DMBA-3,4-diol ...Continue Reading

References

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Nov 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·L M ForresterC R Wolf
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Citations

Jan 5, 1996·Chemico-biological Interactions·A McCordJ A Craft
Aug 26, 1999·Drug Metabolism Reviews·S Ekins, S A Wrighton
Jul 11, 2015·Breast Cancer : Basic and Clinical Research·J Arroyo-AcevedoJosé Ráez-Gonzáles
Jan 12, 2021·Oxidative Medicine and Cellular Longevity·Qiuyuan YangShuguang Chen

Related Concepts

Metazoa
Metabolic Biotransformation
Cytochrome P-450 Oxygenase
Alloenzymes
Microsomes, Liver
August Rats
9,10-Dimethyl-1,2-benzanthracene
Rats, Laboratory

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