Quantifying the impact of diet on carcinogen exposure

量化饮食对致癌物暴露的影响

• 批准号: 6448253
• 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/6448253
• 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 人类癌症的病因。煮熟的肌肉肉包含有效的诱变剂和 属于杂环胺（HA）类的啮齿动物致癌物 化合物。根据对煮熟的肉类的分析，人类暴露于 水平可能超过每十亿美元。虽然我们可以可靠 测量煮熟的肉中存在的量，量化 这些化合物的生物学有效剂量目前受到我们的限制 对个人生理学和 这些致癌物与饮食中其他食物的相互作用。目标 这项研究的是开发一种暴露评估方法，以预测 消化参数，肠运输和饮食对低的影响 剂量暴露于常见的食品致癌物中。特定目标 建议是：1）制定一种体外消化程序来估计 最常见的四个有生物利用度，2）确定 使用人类结肠从消化物中吸收致癌物 癌细胞系CACO2，一种常用的肠吸收模型，3） 确定单一和多种食物相互作用对致癌物的影响 在受控环境中的生物利用度和4）确定生物学上 这些化合物在人类中的有效剂量并验证体外方法。 煮熟的肉将在实验室中消化，并从 肉基质将使用HPLC测量。实验室消化将 然后耦合到CACO-2肠细胞以测量跨 肠细胞壁。使用这种方法，其他食物对HA的影响 生物利用度将通过同时消化肉来确定 蔬菜，水果，液体，碳水化合物和脂肪。最后，结果 将将实验室研究与两项人类研究进行比较，以验证 方法。目前，没有准确的方法来确定 有。这里提出的体外方法可以为您提供宝贵的见解 调节这些化合物的生物利用度的饮食相互作用。 这些实验还将为更准确的暴露提供基础 测量饮食和癌症的流行病学研究。更好的 这些食物致癌物的生物利用剂量的估计和 了解其他食物如何影响生物利用度将使之成为可能 制定有可能降低暴露水平的策略。因为 结果将基于共同食品的相互作用，这些结果可以 轻松地转化为公众。一旦饮食因素的影响是 理解，然后有可能强调预防策略 将消除或修改风险。