Abstract
Two major pathways are responsible for the metabolic activation of benzo[a]pyrene (BP) and other aromatic hydrocarbons, one leading to radical cations and the other to diol epoxides. It has been suggested that 7-hydroxyBP (7-OHBP) might inhibit formation of diol epoxides. We have examined the effect of various concentrations of 7-OHBP on the cytochrome P450-catalyzed metabolism of BP, total DNA binding and formation of BP-DNA adducts. Metabolism of BP was not significantly affected by 7-OHBP. Both total BP-DNA binding and stable DNA adducts, as measured by the 32P-postlabeling method, were inhibited in a concentration-dependent manner, ranging from 25% to 72% inhibition for binding and 23% to 85% for adducts at 7-OHBP:BP ratios of 0.1 to 1.0. Formation of the depurination adducts of BP was inhibited 67% to 100% at a molar ratio of 1:0.25 (BP:7-OHBP), whereas none of the depurination adducts were detected at a molar ratio of 1:0.5 (BP:7-OHBP). These results suggest that 7-OHBP is not a selective inhibitor of the BP diol epoxide pathway, but a potent inhibitor of total DNA adduct formation.
Original language | English (US) |
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Pages (from-to) | 111-118 |
Number of pages | 8 |
Journal | Polycyclic Aromatic Compounds |
Volume | 6 |
Issue number | 1-4 |
DOIs | |
State | Published - Jan 1994 |
Keywords
- 7-hydroxybenzo[a]pyrene
- DNA adducts
- Metabolism
- diol epoxide
- inhibitory effect
- radical cation
ASJC Scopus subject areas
- Organic Chemistry
- Polymers and Plastics
- Materials Chemistry