CORE--BIOMARKER LABORATORY

核心--生物标志物实验室

• 批准号: 6358481
• 负责人: STEPHEN S HECHT
• 金额: $ 23.67万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6358481
• 关键词: behavioral /social science research tag; biomarker; biomedical facility; cancer risk; carcinogenesis; carcinogens; data collection methodology /evaluation; dosage; gas chromatography mass spectrometry; high performance liquid chromatography; human subject; nicotine; oxidative stress; physical chemical interaction; smoking cessation; tobacco abuse; urinalysis

The Biomarker Core provides a unique resource to the TTURC investigators. This Core will provide not only biomarker measurements, but also expertise in the interpretation of these data and their application in the design of further research approaches toward reduction of tobacco associated diseases. The work of this Core is highly integrated into all projects of the TTURC. The expertise of this Core in tobacco carcinogenesis, nicotine biochemistry, and carcinogen metabolism adds an important dimension to this TTURC. The work of the Biomarker Core will center around two main broad themes: 1) measurement of nicotine metabolites and biomarkers of carcinogen uptake to assess the relationship of tobacco exposure at various levels to uptake of nicotine and carcinogens and 2) the relationship of nicotine metabolism, as mediated by cytochrome P450 2A6, to susceptibility to cigarette use. The following alkaloids, metabolites, and adducts will be quantified in this work: nicotine metabolites including nicotine-glucuronide, cotinine, cotinine-glucuronide, trans~3?~ hydroxycotinine, and trans-3'-hydroxycotinine-glucuronide; 7- hydroxycoumarin as a measure of cytochrome P450 2A6 activity; 4- (methylnitrosamino)-l-(3-pyridyl)-l-butanol (NNAL) and its glucuronide (NNAL-Gluc) as measures of uptake of the tobacco-specific lung carcinogen 4-(methylnitrosarnino)-I-(3-pyridyl)-l-butanone (NNK); I- hydroxypyrene as a measure of uptake of carcinogenic polycyclic aromatic hydrocarbons; 4-aminobiphenyl-hemoglobin adducts as indicators of the uptake and metabolic activation of the human bladder carcinogen 4- aminobiphenyl; F2-isoprostanes as indicators of oxidative damage associated with cigarette smoking; and metabolites of NNK as influenced by nicotine administration. Collectively, these biomarkers will substantially enhance our understanding of the biochemical and mechanistic aspects of the tobacco exposure reduction strategies being explored in this TTURC.

生物标志物核心为TTURC研究人员提供了独特的资源。该核心不仅将提供生物标志物测量值，而且还将在解释这些数据的解释及其在设计进一步的研究方法中的应用方面提供专业知识，以减少烟草相关疾病。该核心的工作高度集成到TTURC的所有项目中。这种核心在烟草致癌，尼古丁生物化学和致癌代谢方面的专业知识为这一TTURC增添了重要的维度。生物标志物核心的工作将围绕两个主要主题：1）测量尼古丁代谢物和致癌物摄取的生物标志物，以评估烟草在各种水平上暴露于尼古丁和癌剂的摄取以及2）烟碱代谢的关系的关系。在这项工作中将量化以下生物碱，代谢产物和加合物：包括尼古丁代谢产物，包括尼古丁葡萄糖醛酸，可替氨酸，可替氨酸 - 葡萄糖苷，trans〜3？〜羟基糖蛋白和透射-3'-羟基果蛋白蛋白 - 羟基果素蛋白二甲胺； 7-羟基丙木素作为细胞色素P450 2A6活性的量度； 4-（甲基硝基氨基氨基）-l-（3-吡啶基）-L-丁醇（NNAL）及其葡萄糖醛酸（Nnal-gluc），作为摄取烟草特异性肺癌4--（甲基硝基苯基诺诺省）-I-（3-------- l-l-l-butanone（NNNNNNO）的摄取量。 I-羟基苯乙烯作为致癌多环芳烃摄取的量度； 4-氨基苯基血红蛋白加合物作为人膀胱致癌的摄取和代谢激活的指标； 4-氨基苯基； F2-异前列腺作为与吸烟有关的氧化损伤的指标； NNK的代谢产物受尼古丁给药的影响。总的来说，这些生物标志物将大大增强我们对在此TTURC中探索的烟草暴露策略的生化和机械方面的理解。