Aflatoxin b1 hydroxylation by the pregnenolone-16α-carbonitrile-inducible form of rat liver microsomal cytochrome p-450

Michael R. Halvorson, Steven H. Safe, Andrew Parkinson, Timothy D. Phillips

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

The effects of treating rats with various pregnenolone-16α-carbonitrile (PCN)-type inducers of cytochrome P-450p on the liver microsomal metabolism of aflatoxin B1 (AFB1) were investigated. Treatment of male rats with PCN resulted in a 6-fold increase in the 9-hydroxylation of AFB1 to aflatoxin Q1 (AFQ1). Treatment of female rats with PCN resulted in a 16-fold increase in the formation of AFQ1. The age-dependent decline in constitutive cytochrome P-450p levels in female but not male rats resulted in a sex difference in the formation of AFQ1 in liver microsomes from untreated rats (male: female ∼ 3: 1). The formation of AFQ1 was stimulated up to 5.4-fold when liver microsomes from triacetyloleandomycin (TAO)-treated rats were treated with potassium ferricyanide, which dissociates the complex between cytochrome P-450p and TAO. Treatment of male rats with the cytochrome P-450p inducer, dexamethasone, increased (∼ 7-fold) the 9-hydroxylation of AFB1 to AFQ1 by liver microsomes, and also enhanced (∼ 2-fold) the microsomal activation of AFB1 to metabolites that were mutagenic to Salmonella typhimurium TA98 and TA100. These results indicate that the 9-hydroxylation of AFB1 to AFQ1 is catalyzed by rat liver microsomal cytochrome P-450p.

Original languageEnglish (US)
Pages (from-to)2103-2108
Number of pages6
JournalCarcinogenesis
Volume9
Issue number11
DOIs
StatePublished - Nov 1988

ASJC Scopus subject areas

  • Cancer Research

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