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 在许多流行病学研究中都发现了。 相比之下，临床 为确定β-胡萝卜素（B-β-胡萝卜素）的作用而进行的干预试验， 胡萝卜素）补充对吸烟者肺癌发病率的影响， 接触石棉的工人发现了负面影响。 一些研究表明 高剂量B-胡萝卜素补充剂的致癌反应 在人类干预试验中报告的可能与使用的剂量有关 和/或β-胡萝卜素在富含自由基的环境中的不稳定性 吸烟者的肺。 最近支持番茄红素对风险的保护作用的证据 肺癌和前列腺癌的发病率在人类流行病学 研究和动物研究。 然而，对机械的理解 番茄红素可能的化学预防功效的基础， 需要控制实验条件。 更具体地说， 已知在化学结构上类似于β-胡萝卜素的番茄红素， 具有器官特异性功能;即，番茄红素可能保护前列腺 癌症，但可能与烟草烟雾相互作用，产生意想不到的不利影响， 对肺癌的影响 在这项拟议的研究中，研究人员将调查 番茄红素的化学预防功效在各种不同的 环境（例如，在不同的剂量下，有和没有接触烟草 吸烟，肺与前列腺）。 他们将决定是否 番茄红素摄入量与氧化应激反应之间存在剂量依赖关系， 血浆和组织（肺和前列腺）中的应力。 他们将决定 番茄红素在生理学（低）和药理学上有效性 （高）剂量作为烟雾中的抗增殖剂或增殖剂- 通过检查细胞增殖、p53表达肿瘤 抑制子及其靶基因与肺细胞凋亡的关系。 此外，他们将 在体外检测番茄红素氧化代谢产物的形成， 暴露于烟雾的组织与未暴露于烟雾的肺和前列腺组织 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的组织部位和 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.