Tomatoes, Lycopene, and Prostate Carcinogenesis in Mice

西红柿、番茄红素和小鼠前列腺癌发生

• 批准号: 7318417
• 负责人: JOHN W ERDMAN
• 金额: $ 30.12万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-20 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7318417
• 关键词: Adenocarcinoma; Advertisements; Alternative Medicine; American; Animal Model; Animals; Appendix; Biodistribution; Blood; Cancer Burden; Cancer Model; Carotenoids; Cells; Clinical; Clinical Trials; Consumption; Data; Development; Diet; Dietary Intervention; Dose; Drug or chemical Tissue Distribution; Enzymes; Epidemiologic Studies; Etiology; Evidence based intervention; Evolution; Experimental Models; Future; Genes; Genetic Polymorphism; Goals; Grant; Heterogeneity; Human; Illinois; Individual; Intake; Intervention Studies; Intervention Trial; Knock-out; Knockout Mice; Knowledge; Label; Laboratories; Literature; Malignant Neoplasms; Malignant neoplasm of prostate; Measures; Messenger RNA; Metabolic; Metabolism; Mixed Function Oxygenases; Modeling; Mouse Strains; Mus; Numbers; Ohio; Phytochemical; Play; Powder dose form; Prevention; Principal Investigator; Printing; Production; Prostate; Public Health; Qualifying; Radiolabeled; Relative Risks; Research; Research Personnel; Risk; Rodent; Role; Safety; Scientist; Staging; Structure; Study Section; Suspension Culture; System; Techniques; Television; Testing; Thinking; Time; Tissues; Tomatoes; Transgenic Mice; Transgenic Organisms; Universities; Up-Regulation; Week; Work; anticancer activity; base; cancer risk; carcinogenesis; corticosterone methyl oxidase I; day; design; diet and cancer; feeding; gene interaction; human study; insight; lycopene; mRNA Expression; men; mouse model; novel; phytoene; phytofluene; prevent; programs; prostate cancer prevention; radiotracer; response; tool; tumor progression; tumorigenesis; uptake

DESCRIPTION (provided by applicant): The overall research focus of the collaborative team from the University of Illinois and The Ohio State University has been to determine the impact of tomatoes and their bioactive components, especially lycopene, on prostate carcinogenesis. Prostate cancer is the most common cancer in American men and dietary approaches that reduce risk, or delay onset, would have profound impact on public health. Epidemiological and animal studies suggest that consumption of tomato products reduces the risk of prostate cancer. We propose to carry out studies in transgenic mice to determine if the tomato carotenoids, lycopene, phytoene, and phytofluene, or their metabolic products reduce the risk of development and progression of prostate cancer. In order to answer the questions raised in this proposal, we will utilize two new mouse strains that lack one of the two known mammalian carotenoid cleavage enzymes, carotenoid 15, 15' monooxygenase (CMO-I) and carotenoid 9', 10' monooxygenase (CMO-II). The three major specific aims are: 1) delineate the tissue-specific expression of CMO-I and CMO-II in A) wild-type, CMO-I knockout (KO), and CMO-II KO mice in response to short (3 days) and long term (30 days) feeding of different levels of tomato powder or lycopene, and in B) TRAMP mice during the development of carcinogenesis, 2) precisely determine how changes in CMO-I and CMO-II expression dictate A) tissue biodistribution of tomato carotenoids, and B) production of lycopenoids and other tomato carotenoid metabolites, and 3) to investigate the effect of altered tomato carotenoid metabolism on prostate cancer by A) creating double transgenic mice and B) differentiating the ability of dietary tomato powder and lycopene to inhibit prostate cancinogenesis in TRAMP, TRAMP X CMO-I KO, and TRAMP X CMO-II KO mice. We are uniquely qualified to carry out the proposed studies due to our broad expertise with carotenoids and cancer models, access to CMO-I KO and II KO mice, and our ability to biosynthesize radiolabeled tomato carotenoids using tomato cell suspension culture. Our continuing hypothesis is that genetic polymorphisms involved in metabolism of carotenoids, such as CMO-I and II, are critical determinants of the benefits of tomato products against prostate carcinogenesis in humans. These studies will allow us to determine if tomato carotenoids, or their metabolic products, are able to prevent or counteract the development of prostate cancer.

描述（由申请人提供）：来自伊利诺伊大学和俄亥俄州立大学的合作团队的总体研究重点是确定西红柿及其生物活性成分，特别是番茄红素对前列腺癌的影响。前列腺癌是美国男性中最常见的癌症，降低风险或延缓发病的饮食方法将对公众健康产生深远影响。流行病学和动物研究表明，食用番茄制品可以降低患前列腺癌的风险。我们建议在转基因小鼠中开展研究，以确定番茄类胡萝卜素、番茄红素、植物烯和植物氟素或其代谢产物是否能降低前列腺癌的发生和发展风险。为了回答本文提出的问题，我们将利用两种新的小鼠菌株，它们缺乏两种已知的哺乳动物类胡萝卜素裂解酶，类胡萝卜素15,15 ‘单加氧酶（CMO-I）和类胡萝卜素9’，10'单加氧酶（CMO-II）中的一种。三个主要的具体目标是：1)描述的组织表达CMO-I和CMO-II)野生型,CMO-I淘汰赛(KO),和CMO-II KO小鼠短期(3天)和长期(30天)喂养不同级别的西红柿粉或番茄红素,和B)流浪汉老鼠致癌作用的发展,2)精确确定CMO-I和CMO-II表达的变化决定的)组织biodistribution番茄类胡萝卜素,和B)生产lycopenoids和其他番茄类胡萝卜素代谢产物,3)研究改变番茄类胡萝卜素代谢对前列腺癌的影响，A)建立双转基因小鼠，B)区分日粮番茄粉和番茄红素对TRAMP、TRAMP X CMO-I型KO和TRAMP X CMO-II型KO小鼠前列腺癌发生的抑制能力。由于我们在类胡萝卜素和癌症模型方面的广泛专业知识，获得CMO-I KO和II KO小鼠，以及我们使用番茄细胞悬浮培养生物合成放射性标记的番茄类胡萝卜素的能力，我们具有开展拟议研究的独特资格。我们持续的假设是，参与类胡萝卜素代谢的基因多态性，如cmo - 1和II，是番茄制品对人类前列腺癌有益的关键决定因素。这些研究将使我们能够确定番茄类胡萝卜素或其代谢产物是否能够预防或抵消前列腺癌的发展。