The magnitude of human exposure to BaP through diet has generated a great deal of interest with regard to the association of ingested BaP with gastrointestinal carcinogenesis. Studies conducted in our laboratory have shown that subchronic exposure to BaP through oral administration causes tumors in the colon of ApcMin mice. Given the fact that colon cancer ranks third among cancer-related mortalities, and in US alone around 60,000 lives are lost every year to colon cancer, it is necessary to evaluate the effect of chemopreventive compounds on colon cancer initiation and progression. In this study we investigated the chemopreventive effects of resveratrol on BaP-induced colon carcinogenesis in ApcMin mouse model. The mice were grouped under three treatment categories. For the first group of mice, BaP was administered to mice in peanut oil at a dose of 100 \#956;g/kg via oral gavage over a 60 day period. For the second group of mice, RVT was co-administered with BaP at a dose of 45 \#956;g/kg. A solution containing 10% ethanol + 90% deionized water served as vehicle for RVT. The third group of mice received RVT only. Appropriate vehicle controls were maintained for the treatment categories. Blood, jejunum, colon and liver, were collected at 60 days post-BaP & RVT exposure; adenomas in jejunum and colon were counted and subjected to histopathology. Resveratrol significantly inhibited the development of adenomas in jejunum and colon by 45% and 40% (P < 0.001) respectively. Though not much of a difference was observed in the size of adenomas in jejunum of BaP + RVT-treated mice, compared to that of BaP-treated mice; the colon samples showed a different trend. Resveratrol reduced the size of colon adenomas in BaP + RVT-treated mice significantly compared to mice that received BaP alone. While dysplasia of varying degrees was noted in colon of BaP-treated mice, the dysplasias\#8217; were of limited occurrence in RVT-treated mice. Our observations reveal that RVT inhibits colon tumorigenesis when given together with BaP. Studies are in progress to see if this preventive effect is dose-dependent both for the chemopreventive agent and the carcinogen (supported by NIH grants RO3CA130112-01, 5T32 HL007735-14 and S11ES014156).
Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 955.
100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO