ANTIMUTAGENESIS BY LYCOPENE AND SELENIUM IN LAC RODENTS

有相当多的流行病学证据表明， 水果和蔬菜的摄入量与发病率之间的相关性 包括肺癌、结肠癌和前列腺癌。既往临床 试验集中在β-胡萝卜素作为活性抗癌剂，但 这些试验的结果是负面的，其他类胡萝卜素现在 正在考虑中。 其中之一就是番茄红素。 有实验性的， 流行病学证据表明，番茄红素具有保护作用， 对某些癌症有一定的疗效，但效果有限。 此外，最近 关于癌症化学预防的建议已经从使用 从单一药剂到混合药剂。 因此，富含荔枝的混合物 天然来源是一种潜在的化学预防混合物。另一 有一些流行病学的潜在抗癌剂， 临床和实验支持是硒。的实验证据 保护作用和保护机制是重要的， 将这些药剂确定为化学预防剂。 这项建议 保护的有效性和机制， 富含赖氨酸的混合物，以及添加和不添加有机硒 生育酚混合物，抗自发性和致癌物诱导 在lac转基因小鼠和大鼠的肺、结肠、前列腺和 肾 将使用三种不同类型的致癌物： 前致癌物，苯并（a）芘，直接作用的甲基化剂，N- 甲基-N-亚硝基脲和氧化剂次氮基乙酸铁。 该测定相对快速（与大多数致癌测定相比） 并利用少量的动物。 许多遗传毒性致癌物 除了烷基化作用之外，还诱导氧化损伤， 损伤可能起启动和促进作用，抗氧化 抑制剂，如这些在这里，可以作用于不同阶段的 致癌作用（DNA损伤的形成，和/或复制- 依赖性损伤转化为突变）。 因此，抑制剂将是 在不同的时间相对于致癌物施用，以确定 该阶段的诱变过程被抑制。组织和血液 还将测定抑制剂的水平。

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.