ANTIMUTAGENESIS BY LYCOPENE AND SELENIUM IN LAC RODENTS

有相当多的流行病学证据表明情况相反 果蔬摄入量与发病率的相关性研究 包括肺癌、结肠癌和前列腺癌。既往临床 试验的重点是β-胡萝卜素作为活性抗癌剂，但 这些试验的结果是阴性的，其他类胡萝卜素现在是 正在考虑中。其中之一就是番茄红素。有试验性的和 流行病学证据表明，番茄红素具有保护作用 对某些癌症有效，但它是有限的。另外，最近 关于癌症化学预防的建议已经从使用 从单一试剂到混合物。因此，富含番茄红素的混合物来自 天然资源代表了一种潜在的化学预防混合物。另一个 潜在的抗癌药物，其具有一定的流行病学， 临床和实验支持是硒。实验证据表明 保护效果和保护机制在以下方面很重要 将这些药物确定为化学预防药物。这项建议 解决了通过以下方式保护的有效性和机制 富含番茄红素的混合物和添加和不添加的有机硒 生育酚混合物，抗自发性和致癌物诱导 Lac转基因小鼠和大鼠肺、结肠、前列腺和 肾脏。将使用三种不同类型的致癌物质： 前致癌物，苯并(A)芘，直接作用甲基化试剂，N- 甲基-N-亚硝脲和氧化剂硝酸铁。 该检测相对较快(与大多数致癌检测相比) 并利用少量的动物。与许多具有遗传毒性的致癌物 除了烷基化还会引起氧化损伤，这样的氧化 损伤可能在启动和促进抗氧化剂中发挥作用 像这里这样的抑制剂，可能作用于不同阶段的 致癌(DNA损伤的形成，和/或复制- 依赖于将损伤转化为突变)。因此，抑制剂将是 相对于致癌物在不同的时间给药以确定 突变过程的哪一阶段被抑制。组织和血液 抑制剂的水平也将被确定。

There is considerable epidemiological evidence showing inverse correlations between intake of fruits and vegetables and the incidence of certain cancers including lung, colon and prostate. Previous clinical trials have focused on beta-carotene as the active anticancer agent, but results of these trials were negative and other carotenoids are now being considered. One of these is lycopene. There is experimental and epidemiological evidence suggesting that lycopene has a protective effect against certain cancers, but it is limited. Also, recent recommendations on cancer chemoprevention have shifted from the use of single agents to mixtures. Therefore, lycopene-rich mixtures from natural sources represent one potential chemopreventative mix. Another potential anticancer agent for which there is some epidemiological, clinical and experimental support is selenium. Experimental evidence for protective effects and for a mechanism of protection are important in establishing these agents as chemopreventatives. This proposal addresses both the effectiveness and the mechanism of protection by a lycopene-rich mixture, and organic selenium with and without added tocopherols mixture, against spontaneous and carcinogen-induced mutagenesis in lac transgenic mice and rats in lung, colon, prostate and kidney. Three different types of carcinogens will be employed: the procarcinogen, benzo(a)pyrene, the direct-acting methylating agent, N- methyl-N-nitrosourea, and the oxidative agent ferric-nitriloacetate. The assay is relatively rapid (compared to most carcinogenesis assays) and utilizes small numbers of animals. as many genotoxic carcinogens induce oxidative damage in addition to alkylation, and such oxidative damage may play a role in initiation and promotion, antioxidant inhibitors such as those here, may act on different stages of carcinogenesis (the formation of DNA damage, and/or the replication- dependent conversion of damage to mutations). Thus, inhibitors will be administered at different times relative to carcinogens to determine which stage of the mutagenesis process is inhibited. Tissue and blood levels of inhibitors will also be determined.