## Abstract The potent carcinogen benzo[a]pyrene (B[a]P) and its metabolite B[a]P __trans__‐7, 8‐dihydrodiol (7, 8‐diol) require metabolic activation by the microsomal cytochrome P450s (P450s) to exert several adverse biological effects, including binding to DNA, toxicity, mutagenicity, and carcino
Activation of benzo(a)pyrene-7,8-dihydrodiol in rat uterus: Anin vitro study
✍ Scribed by Byczkowski, Janusz Z. ;Kulkarni, Arun P.
- Publisher
- John Wiley and Sons
- Year
- 1990
- Tongue
- English
- Weight
- 673 KB
- Volume
- 5
- Category
- Article
- ISSN
- 0887-2082
No coin nor oath required. For personal study only.
✦ Synopsis
Peroxidatic metabolism of benzo( a ) pyrene-7,S-dihydrodiol by calcium containing extracts of rat uteri was investigated. Covalently bound and soluble metabolites of benzo( a)pyrene-7,S-dihydrodiol were quantitated by radiometry and high performance liquid chromatography, respectively. 1. Uterine extracts incubated with benzo( a)pyrene-7,s-dihydrodiol activated this proximate mutagen to protein binding metabolite(s). 2. Hydrogen peroxide increased the protein binding and yielded a substantial amount of benzo( a ) pyrene-trans-anti-tetrahydrotetrol, suggesting the peroxyl-type free-radical epoxidation process. 3. The results indicate that rat uterine peroxidase is able to catalyze free-radical activation of benzo ( a)pyrene4,8-dihydrodiol by epoxidation to its 9,10-dihydrodiolepoxide, a known ultimate mutagen and carcinogen.
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