Effect of Cancer Chemopreventive Agents on DNA Adduct Formation by the Dietary Prostate Carcinogen PhIP

摘要

This goal of this proposal was to investigate chemopreventive strategies to reduce the genotoxic effects of the prostate carcinogen 2- amino- 1-methyl-6-phenylim idazo4,5-Bpyridine (PhIP). PhIP is considered to pose a significant prostate cancer risk to humans because it is found in cooked meat and epidemiology studies have linked meat consumption to prostate cancer. Importantly, PhIP causes prostate cancer in rats following high-dose exposures. Our purpose was to use the rat model to determine the risk posed by PhIP at levels found in the diet and to identify candidate chemopreventive agents for PhIP. Over the period of this grant, we have established that PhIP forms DNA adducts in the prostate and DNA adduct levels are dose-dependent. We have identified PEITC and chorophyllin as potential chemopreventive agents for PhIP and have established potential mechanisms of action. Wine, quercetin, genistein and lycopene have also been investigated, although they did not reduce adduct formation. Follow-on funding has been obtained from NIH, in which we will determine if PEITC and chlorophyll in reduce PhIP-induced prostate tumor formation. We also hope to translate this research in to a treatment that can be used in people (a recently submitted NIH Spore grant with the UC Davis Medical Center, Sacramento, CA).