ACETYLATION AND N-OXIDATION IN COLORECTAL CANCER

一项病例对照研究，以检查患者的独立和联合作用 芳胺乙酰化状态和N-氧化状态与杂环和 芳香胺暴露对结直肠癌发病风险的影响 是提议的。 这项赠款申请的具体目标是： 确认我们关于角色的初步研究的初步结果 杂环和芳香胺的代谢和暴露可能 饮食或环境中的危险因素。来源胺 代谢和暴露是饮食或饮食中的潜在危险因素 环境。杂环胺和芳香胺的来源是 研究了吸烟、饮食和烹饪方法；新陈代谢 有待研究的途径包括杂环胺N-氧化状态和 O-乙酰化状态。 实验设计涉及芳胺的传导。 慢性支气管炎患者乙酰转移酶和芳胺N-氧化表型的研究 有结直肠癌病史的患者和对照组。这 表型鉴定将使用单剂量的咖啡因进行 作为速溶咖啡饮料服用，将涉及收集 一份尿液样本。咖啡因的代谢物将被测量 用高效液相色谱法和AFMU/1X比值测定表型 N-氧化反应为乙酰化反应和[17U+17X]/137X反应。 接触的来源将通过使用威利特食品来确定 提供总能量估计值的频率问卷 摄入量和微量营养素。有关特定项目的其他信息 暴露于胺的情况将在一次个人采访中收集，采访内容包括 吸烟史、饮食习惯(例如，炭烤、烘烤或 微波肉)、职业史、病史和家族史 基本的人口统计信息。 我们假设杂环胺和芳香胺是冒号 对人类来说是致癌物质。这些化合物主要存在于煮熟的鱼中。 和肉类，也存在于香烟烟雾中。基于以下结果： 我们的初步研究，我们假设最易受影响的群体 因为结直肠癌的发展将会是那些 快速乙酰化和快速N-氧化表型，暴露于 到高水平的芳胺，例如红蜜酒煮的做得好。 这项研究应提供有关个人风险的信息。 可以作为尝试修改高风险的基础的因素 这些人的行为(如环境暴露和饮食习惯) 罹患癌症的风险最大。这是一个独特的机会 实验室科学家与传统科学家之间的合作 流行病学家正在开发一种新的癌症风险方法 身份证明。

A case-control study to examine the independent and combined efforts of arylamine acetylator status and N-oxidation status and heterocyclic and aromatic amine exposure on the risk of development of colorectal cancer is proposed. The specific aims of this grant application are: To confirm the initial findings of our pilot study regarding the roles of heterocyclic and aromatic amine metabolism and exposure as putative risk factors from the diet or the environment. The sources amine metabolism and exposure as putative risk factors from the diet or the environment. The sources of heterocyclic and aromatic amines to be studied are cigarette smoking, diet and cooking methods; the metabolic pathways to be studied include heterocyclic amine N-oxidation status and O-acetylation status. The experimental design involves the conduct of arylamine acetyltransferase and arylamine N-oxidation phenotyping on patients with a history of carcinoma of the colorectum and on control patients. This phenotyping will be performed using a single dose of caffeine administered as an instant coffee drink and will involve the collection of a single urine specimen. The caffeine metabolites will be measured by HPLC and the phenotype determined by the radio of AFMU/1X for acetylation and [17U+17X]/137X for N-oxidation. The source of exposure will be determined by the use of the Willett Food Frequency Questionnaire which will provide estimates of total energy intake and micronutrients. Additional information regarding specific exposure to amines will be gathered in a personal interview that covers smoking history, dietary practices (e.g., char-broiled, roasted or microwaved meat), occupational history, medical and family history and basic demographic information. We hypothesize that heterocyclic and aromatic amines are colon carcinogens for humans. These compounds occur primarily in cooked fish and meat and are also present in cigarette smoke. Based on results from our pilot study, we hypothesize that the group at greatest susceptibility for the development of colorectal cancer will be those people who are both rapid acetylation and rapid N-oxidation phenotypes, who are exposed to high levels of arylamines, for example, red mead cooked well done. This study should provide information on relevant individual risk of factors that could serve as a basis for attempts to modify high risk behavior (e.g., environmental exposure and dietary practices) among those at greatest risk to develop cancer. It is a unique opportunity for collaboration between laboratory scientist and traditional epidemiologists in developing a new approach to cancer risk identification.