CANCER CHEMOPREVENTIVE AGENTS ON DNA ADDUCT BY DIETARY PROSTATE CARCINOGEN PHIP

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 前列腺癌是男性癌症死亡的主要原因，但这种疾病发展的主要因素在很大程度上仍然不明。 分析人群癌症发病率的研究表明，某些饮食成分，如肉类，会增加前列腺癌的风险。 相比之下，西红柿、绿色蔬菜、维生素E和矿物质硒可以降低风险。 尽管富含水果和蔬菜而少吃肉的饮食似乎是有益的，但几乎没有直接证据支持这些发现或解释饮食因素在前列腺癌发展中的作用。 目前用于评估潜在致癌物的生物效应和化学预防剂的有效性的动物模型通常采用高致癌物剂量，这与饮食中遇到的低水平几乎没有生物相关性。 然而，使用环境中可能遇到的致癌物剂量进行调查是困难的，需要使用非常敏感的测定。 加速器质谱是一种能够测量痕量化学品的高灵敏度技术。 AMS将用于确定烹饪过程中肉类中形成的膳食致癌物是否是饮食暴露水平下的前列腺癌风险因素。 PhIP已被证明会导致DNA损伤（癌症发展的初始步骤），并在高剂量后诱导大鼠前列腺肿瘤。 这些观察结果，加上肉类消费增加了前列腺癌的风险，进一步强调了PhIP在人类前列腺癌发展中的潜在作用。 通过AMS测定了暴露于饮食相关剂量的PhIP后大鼠前列腺中的DNA损伤量。 然后，我们评估了化学预防剂番茄红素（番茄的一种成分），叶绿酸，异硫氰酸酯PEITC和染料木素在减少DNA损伤量方面的有效性。 因此，这项工作确定了肉类中的致癌物质可能在低剂量下导致前列腺癌，并帮助确定了有效的化学预防策略。

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.