Quantifying the impact of diet on carcinogen exposure

量化饮食对致癌物暴露的影响

• 批准号: 6522772
• 负责人: JAMES S. FELTON
• 金额: $ 24.5万
• 依托单位: UNIVERSITY OF CALIF-LAWRNC LVRMR NAT LAB
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6522772
• 关键词: P glycoprotein; chemical carcinogen; chemical carcinogenesis; clinical research; gastrointestinal absorption /transport; heterocyclic compounds; high performance liquid chromatography; human subject; meat; nutrition aspect of cancer; nutrition related neoplasm /cancer; nutrition related tag; tissue /cell culture; urinalysis; vegetables

DESCRIPTION (provided by applicant): Human epidemiologic and animal studies have shown that diet has a role in the etiology of human cancer. Cooked muscle meats contain potent mutagens and rodent carcinogens belonging to the heterocyclic amine (HA) class of compounds. Based on analyses of cooked meats, humans are exposed to HAs at levels that may exceed a hundred parts-per-billion. Although we can reliably measure the amount of HAs present in cooked meats, quantifying the biologically effective dose of these compounds is currently limited by our imperfect understanding of the effects of individual physiology and the interactions of these carcinogens with other foods in the diet. The objective of this study is to develop an exposure assessment method that will predict the effect of digestion parameters, intestinal transport and diet upon the low dose exposure to commonly ingested food carcinogens. The specific aims of the proposal are: 1) develop an in vitro digestion procedure to estimate the bioavailability of the four most commonly occurring HAs, 2) determine the absorption of the carcinogens from the digestates using the human colon carcinoma cell line Caco2, a commonly used model for intestinal absorption, 3) determine the effects of single and multiple food interactions on carcinogen bioavailability in a controlled environment and 4) determine the biologically effective dose of these compounds in humans and validate the in vitro method. Cooked meats will be digested in the laboratory and HAs made available from the meat matrix will be measured using HPLC. The laboratory digestates will then be coupled to Caco-2 intestinal cells to measure transport across the intestinal cell wall. Using this method the effect of other foods on HA bioavailability will be determined by digesting the meat concurrently with vegetables, fruits, liquids, carbohydrates, and fats. Finally, the results of the laboratory study will be compared to two human studies to validate the method. At present there is no accurate way to determine bioavailability of HAs. The in vitro method proposed here could provide valuable insight into the dietary interactions that modulate the bioavailability of these compounds. These experiments will also provide a basis for more accurate exposure measurements for epidemiological investigations of diet and cancer. Better estimates of the bioavailable dose of these food carcinogens and an understanding of how other foods affect bioavailability will make it possible to devise strategies that could potentially reduce exposure levels. Because the results will be based upon interactions of common foods, these results can be easily translated to the public. Once the impact of dietary factors is understood, then it will be possible to emphasize prevention strategies that will eliminate or modify the risk.

描述(由申请人提供)： 人类流行病学和动物研究表明，饮食在 人类癌症病因学。煮熟的肌肉肉含有有效的诱变剂和 属于杂环胺(HA)类的啮齿动物致癌物 化合物。根据对熟肉的分析，人类暴露在HAS中 可能超过十亿分之一百的水平。尽管我们可以可靠地 测量熟肉中存在的HAS的数量，量化 这些化合物的生物有效剂量目前受到我们的 对个体生理学影响的认识不完善 这些致癌物质与饮食中其他食物的相互作用。目标是 这项研究的目的是开发一种暴露评估方法，该方法将预测 消化参数、肠道转运和饮食对低血糖的影响 暴露于经常摄入的食物致癌物质。《公约》的具体目标 建议是：1)开发一种体外消化程序来估计 四种最常见的生物利用度，2)决定了 利用人体结肠吸收消化液中的致癌物 癌细胞系Caco 2，一种常用的肠道吸收模型，3 确定单一和多种食物相互作用对致癌物质的影响 在受控环境中的生物利用度和4)生物决定 这些化合物在人体内的有效剂量，并验证体外方法。 熟肉将在实验室消化，并已从 肉的基质将用高效液相色谱仪进行测定。实验室的消化系统将 然后与Caco-2肠道细胞偶联以测量跨 肠道细胞壁。用此法测定其他食物对透明质酸的影响 生物利用度将通过同时消化肉类和 蔬菜、水果、液体、碳水化合物和脂肪。最后，结果是 这项实验室研究将与两项人体研究进行比较，以验证 方法。目前还没有准确的方法来确定阿司匹林的生物利用度 有过。这里提出的体外方法可以提供有价值的洞察 调节这些化合物的生物利用度的饮食相互作用。 这些实验也将为更准确的曝光提供基础。 饮食和癌症流行病学调查的测量。更好 估计这些食品致癌物质的生物可利用剂量和 了解其他食物如何影响生物利用度将使之成为可能。 制定可能降低暴露水平的策略。因为 结果将基于常见食物的相互作用，这些结果可以 很容易被翻译给公众。一旦饮食因素的影响是 理解，那么就有可能强调预防战略， 将消除或修改风险。