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

Abstract : This proposal aims to investigate chemopreventive strategies to reduce the genotoxic effects of the prostate carcinogen 2-amino-I- methyl-6-phenylimidazo4,5-Bpyridine (PhIP). PhIP is considered to pose a significant prostate cancer risk to humans because it is found in cooked mcat and epidemiology studies have linked meat consumption to prostate cancer. Importantly PhIP causes prostate cancer in rats 101 lowing high-dose exposures. Therefore our purpose is to use the rat model to determine the risk posed by PhIP at levels found in the diet and to identify candidate chemopreventive effects that could be used to reduce prostate cancer risk as a result to exposure to PhIP. Over the last year, we have established several mechanisms by which the isothiocyanate PEITC reduce the genotoxic effects of PhIP and have investigated the dose-dependence of the chemopreventive effects . We have completed experiments using chlorophyllin arid lycopene and have shown that chlorohyllin may also be useful in prostate cancer prevention. Importantly, albumin adduct levels in the blood were useful biomarkers of these chemopreventive effects. Consequently, this work may lead to the identification of effective chemopreventive strategies.