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Stereoselectivity of Rat Liver Cytochrome P-450 Isozymes: Direct Determination of Enantiomeric Composition of K-Region Epoxides Formed in the Metabolism of Benz[A]Anthracene and 7,12-Dimethylbenz[A]Anthracene

  • S. K. Yang
  • M. Mushtaq
  • P.-L. Chiu
  • H. B. Weems
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 197)

Abstract

The K-region 5,6-epoxides of benz[a]anthracene (BA) and 7,12-dimethylbenz[a]anthracene (DMBA) were isolated by normal-phase HPLC from metabolites formed by incubation of the respective parent compound with liver microsomes from untreated (control), phenobarbital (PB)-treated, and 3-methylcholanthrene (MC)-treated rats in the presence of an epoxide hydrolase inhibitor, 3,3,3-trichloropropylene 1,2-oxide. The enantiomeric contents of the metabolically formed K-region 5,6-epoxides of BA and DMBA were directly determined by chiral stationary phase HPLC. The K-region 5,6--epoxides formed in the metabolism of BA have (5R,6S): (5S,6R) enantiomer ratios of 25:75 (control), 21:79 (PB), and 4:96 (MC), respectively. In contrast, the (5R,6S):(5S,6R) enantiomeric ratios of the K-region 5,6-epoxides formed in the metabolism of DMBA are 76:24 (control), 80:20 (PB), and 97:3 (MC), respectively. These and earlier results on the stereoselective K-region metabolism studies of 7methylbenz[a]anthracene and 12-methylbenz[a]anthracene indicate that (i) cytochrome P-450 isozymes exhibit different stereoselectivities in the K-region epoxidations of BA and DMBA and (ii) a methyl substituent at the C12 position of BA alters the stereoheterotopic interactions between cytochrome P-450 isozymes and the BA molecule.

Keywords

Polycyclic Aromatic Hydrocarbon Liver Microsome Epoxide Hydrolase Enantiomer Ratio Enantiomeric Composition 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • S. K. Yang
    • 1
  • M. Mushtaq
    • 1
  • P.-L. Chiu
    • 1
  • H. B. Weems
    • 1
  1. 1.Department of Pharmacology, F. Edward Hébert School of MedicineUniformed Services University of the Health SciencesBethesdaUSA

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