CANCER CHEMOPREVENTIVE AGENTS ON DNA ADDUCT BY DIETARY PROSTATE CARCINOGEN PHIP

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Prostate cancer is a leading cause of cancer death in men, yet the major factors in the development of this disease remain largely unidentified. Studies analyzing cancer incidence in populations have indicated that certain dietary constituents, such as meat, enhance prostate cancer risk. In contrast, tomatoes, green vegetables, vitamin E and the mineral selenium reduce risk. Although a diet high in fruits and vegetables and low in meat appears beneficial, there is little direct evidence to support these findings or to explain a role for dietary factors in the development of prostate cancer. Current animal models used to assess the biological effects of potential carcinogens and the effectiveness of chemopreventive agents typically employ high carcinogen doses, which are of little biological relevance to the low levels encountered in the diet. However, investigations employing carcinogen doses likely to be encountered in the environment are difficult and require the use of very sensitive assays. Accelerator mass spectrometry is a highly sensitive technique capable of measuring trace amounts of chemicals. AMS will be used to determine if a dietary carcinogen formed in meat during cooking is a prostate cancer risk factor at dietary-levels of exposure. PhIP has been shown to cause DNA damage (an initial step in the development of cancer) and induce prostate tumors in rats following high doses. These observations, coupled with the enhanced risk of prostate cancer from the consumption of meat, further emphasizes the potential role for PhIP in the development of prostate cancer in humans. The amount of DNA damage in the prostate of rats following exposure to dietary-relevant doses of PhIP has been determined by AMS. We then assessed the effectiveness of the chemopreventive agents lycopene (a component of tomatoes), chlorophyllin, the isothiocyanate PEITC and genistein in reducing the amount of DNA damage. Consequently, the work determined that a carcinogen in meat may cause prostate cancer at low doses and has helped identify effective chemoprevention strategies.