ANTIMUTAGENESIS BY LYCOPENE AND SELENIUM IN LAC RODENTS

番茄红素和硒对紫胶啮齿动物的抗突变作用

基本信息

批准号：
6283339
负责人：
JOSEPH B GUTTENPLAN
金额：
$ 2.18万
依托单位：
NEW YORK UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-08-15 至 2001-07-31
项目状态：
已结题

项目摘要

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.

有大量的流行病学证据表明逆摄入水果和蔬菜与发病率之间的相关性包括肺，结肠和前列腺在内的某些癌症。以前的临床试验的重点是β-胡萝卜素作为活性抗癌剂，但这些试验的结果为阴性，其他类胡萝卜素现在为被考虑。其中之一是番茄红素。有实验和流行病学证据表明番茄红素具有保护性对某些癌症的影响，但这是有限的。另外，最近关于癌症化学预防的建议已从使用单一的混合物。因此，来自天然来源代表一种潜在的化学预防混合物。其他潜在的抗癌剂，有一些流行病学，临床和实验支持是硒。实验证据保护作用和为保护机制很重要将这些药物确立为化学预防剂。这个建议解决了通过富含番茄红素的混合物和有机硒，没有和不添加生育酚的混合物，与自发性和致癌物诱导的混合物 LAC转基因小鼠和肺，结肠，前列腺和大鼠的诱变肾。将采用三种不同类型的致癌物： procarcinegen，苯并（A）pyrene，直接作用甲基化剂N- 甲基-N-硝酸甲基和氧化剂硝基乙酸铁。该测定相对较快（与大多数癌变测定相比）并利用少量动物。许多遗传毒性致癌物除烷基化外，还诱导氧化损伤，这种氧化损害可能在启动和促进，抗氧化剂中起作用诸如此处的抑制剂可能在不同阶段的行动致癌作用（DNA损伤的形成和/或复制 - 损害转换为突变）。因此，抑制剂将是相对于致癌物的不同时间给药以确定诱变过程的哪个阶段被抑制。组织和血液还将确定抑制剂的水平。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Comparative mutagenicities of bleomycin and ferric-nitrilotriacetate in lacZ mice.

博莱霉素和次氮基三乙酸铁对 lacZ 小鼠的致突变性比较。

DOI：
10.1016/s0304-3835(02)00382-8
发表时间：
2002
期刊：
Cancer letters
影响因子：
9.7
作者：
Kosinska,Wieslawa;Pelle,Edward;vonPressentin,MarciadM;Chen,Michael;Guttenplan,JosephB
通讯作者：
Guttenplan,JosephB

Mutagenesis induced by benzo[a]pyrene in lacZ mouse mammary and oral tissues: comparisons with mutagenesis in other organs and relationships to previous carcinogenicity assays.

lacZ 小鼠乳腺和口腔组织中苯并[a]芘诱导的诱变：与其他器官诱变的比较以及与先前致癌性测定的关系。