Biologic Activity of Lycopene

描述(由申请人提供) 富含类胡萝卜素的水果和蔬菜对癌症风险的有益作用 已在许多流行病学研究中发现。相比之下，临床上 为确定β-胡萝卜素(B-胡萝卜素)的效果而进行的干预试验 胡萝卜素)补充剂对吸烟者或 接触石棉的工人发现了负面影响。多项研究表明 补充高剂量B-胡萝卜素的致癌反应 在人类干预试验中报告的可能与使用的剂量有关 和/或B-胡萝卜素在富含自由基的环境中的不稳定性 吸烟者的肺部。 最近的支持证据表明番茄红素对风险具有保护作用 肺癌和前列腺癌在人类流行病学中都有报道 研究和动物研究。然而，对机械论的理解 番茄红素在井下可能的化学预防效果的基础 需要控制实验条件。更具体地说，它不是 已知在化学结构上与B-胡萝卜素相似的番茄红素， 具有器官特有的功能；即番茄红素可能预防前列腺癌 癌症，但可能与烟草烟雾相互作用，产生意想不到的不良反应 对肺癌的影响。 在这项拟议的研究中，研究人员将研究其机理基础 对于番茄红素在各种不同条件下的化学预防效果 环境(例如，在不同的剂量下，接触和不接触烟草 在雪貂模型中，吸烟、肺和前列腺)。他们将决定是否 番茄红素摄入和氧化之间存在剂量依赖关系。 血浆和组织(肺和前列腺)的应激。他们将决定 番茄红素在生理(低)和药理上的有效性 (高)烟雾中作为抗增殖剂或增殖剂的剂量- 暴露雪貂通过检测细胞增殖、肿瘤组织中P53的表达 抑制子及其靶基因与肺组织细胞凋亡。此外，他们还将 番茄红素体外氧化代谢产物的研究 烟雾暴露与非烟雾暴露大鼠肺和前列腺组织的比较 雪貂。 这些研究将为未来的潜在用途提供重要信息 番茄红素作为癌症预防营养素在不同组织部位的研究 了解烟草可能产生的不良影响。

DESCRIPTION (provided by applicant) Beneficial effects of carotenoid-rich fruits and vegetables on cancer risk have been found in many epidemiological studies. In contrast, clinical intervention trials conducted to determine the effect of Beta-carotene (B- carotene) supplementation on the incidence of lung cancer in smokers or asbestos-exposed workers found a negative effect. Several studies indicate that the carcinogenic response to high dose B-carotene supplementation reported in the human intervention trials may be related to the dosage used and/or the instability of the B-carotene in the free radical-rich environment of the lungs of cigarette smokers. Recent supporting evidence for a protective role of lycopene against the risk of lung and prostate cancer has been reported in both human epidemiologic studies and animal studies. However, an understanding of the mechanistic basis for the possible chemopreventive efficacy of lycopene under well- controlled experimental conditions is needed. More specifically, it is not known whether lycopene, which is similar to B-carotene in chemical structure, has organ specific functions; i.e., lycopene might protect against prostate cancer but may interact with tobacco smoke to produce an unexpected adverse effect on lung cancer. In the proposed study, the researchers will investigate the mechanistic basis for the chemopreventive efficacy of lycopene under a variety of different circumstances (e.g., at varying doses, with and without exposure to tobacco smoke, lung versus prostate) in the ferret model. They will determine if there is a dose-dependent relationship between lycopene intake and oxidative stress in both plasma and tissue (lung and prostate). They will determine the effectiveness of lycopene at both a physiologic (low) and a pharmacologic (high) dose as an antiproliferative or proliferative agent in the smoke- exposed ferret by examining cell proliferation, expression of p53 tumor suppressor and its target gene, and apoptosis in lung. In addition, they will examine the formation of oxidative metabolites of lycopene in vitro in the tissue of smoke-exposed versus non smoke-exposed lung and prostate tissues of ferrets. These studies will provide important information for the potential future use of lycopene as cancer preventive nutrient at different tissue sites and the knowledge of possible adverse effects with tobacco.