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 language | English (US) |
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Pages (from-to) | 2103-2108 |
Number of pages | 6 |
Journal | Carcinogenesis |
Volume | 9 |
Issue number | 11 |
DOIs | |
State | Published - Nov 1988 |
ASJC Scopus subject areas
- Cancer Research