Abstract 5459: Benzo(a)pyrene biotransformation enzyme expression, activities and metabolite disposition in ApcMin mouse colon and liver is altered by resveratrol exposure.

Abstract

Abstract Statistics released by the American Cancer society indicates that colon cancer is the third leading cause of cancer cases and related deaths in America. In addition to dietary preferences and lifestyle habits, exposure to toxicants such as benzo(a)pyrene (BaP) is one of the major contributing factors to the development of sporadic colon cancer. Our laboratory has validated the ApcMin mouse model to study BaP-induced colon carcinogenesis. Ongoing studies in our laboratory are focused towards elucidating the anticarcinogenic effects of resveratrol (RVT) against colon tumors. Our studies thus far have shown a decrease in the incidence, size, and number of adenomas formed in the colon of mice exposed to BaP and RVT, compared to BaP exposure alone. Since biotransformation of toxicants is one of the key steps for initiating carcinogenesis, the objective of this study was to investigate whether RVT exposure simultaneously or prior to BaP treatment alters BaP biotransformation and bioavailability in ApcMin mice. The BaP treatment consisted of BaP-only administration (in peanut oil) at a dose of 100 μg/kg body weight (bw) via oral gavage over a 60 day period (group I); BaP (100 μg/kg bw) co-administered with RVT (in 10% ethanol + 90% deionized water) at a dose of 45 μg/kg bw (group II); RVT administered for 1 week prior to BaP dosing (group III). Blood, colon and liver samples were collected at the end of exposure period. The expression of BaP biotransformation enzymes (CYP1A1, CYP1B1 and GST) in liver and colon were assayed at the level of protein and enzyme activities. Plasma, liver and colon tissue samples were analyzed by reverse phase-HPLC for BaP metabolites. Resveratrol exposure both prior to- and concurrent with BaP exposure caused a decrease in the expression and activity of CYP1A1/1B1 enzymes and an increase in GST enzymes both in liver and colon. Additionally, our studies revealed a decrease in concentrations of organic (Phase I) metabolites in plasma, liver and colon in mice that received RVT + BaP compared to mice that received RVT alone. In contrast, an opposite trend was noted with aqueous (Phase II) metabolites registering an increase in mice that received RVT + BaP compared to mice that received RVT alone. Between the two RVT-treatment strategies, concurrent administration of RVT appeared to limit BaP bioactivation compared to RVT treatment prior to BaP exposure. In summary, our results suggest that RVT provides a preventive effect against BaP-induced colon cancer initiation and progression in ApcMin mice (funded by NIH grants 5T32HL007735-12, 1F31ES019432-01A1 and 5RO1CA142845-O2). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5459. doi:1538-7445.AM2012-5459