Core 3 - Biomarkers and Product Evaluation

核心 3 - 生物标志物和产品评估

• 批准号: 10628258
• 负责人: SHARON E MURPHY
• 金额: $ 7.31万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-03 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10628258
• 关键词: 2-butenal; Acetylcysteine; Acids; Acrolein; Acrylonitrile; Adolescent; Aerosols; Benzene; Biological; Biological Markers; Body Fluids; Carcinogens; Characteristics; Cigarette; Cohort Studies; Cotinine; Cytochrome P450; Data; Dinoprostone; Dose; Electronic cigarette; Evaluation; Exposure to; F2-Isoprostanes; Goals; Health; Individual; Individual Differences; Inflammation; Life; Liquid substance; Measurement; Measures; Metabolic; Metabolism; Methods; Minnesota; Nicotine; Oxidative Stress; Participant; Pathway interactions; Persons; Phenotype; Plasma; Population; Property; Protocols documentation; Reporting; Research; Risk Assessment; Saliva; Salivary; Sampling; Sensitivity and Specificity; Services; Smoker; Standardization; Sum; Technology; Time; Tobacco use; Tobacco-Associated Carcinogen; Toxicant exposure; Universities; Urine; Visit; Volatilization; adolescent health; biomarker validation; cigarette smoking; electronic cigarette use; electronic cigarette user; electronic liquid; hydroxycotinine; indexing; multidisciplinary; nicotine exposure; nicotine use; non-smoker; oxidation; oxidative damage; programs; saliva sample; success; tobacco exposure; tobacco products; tobacco toxicant; toxicant; urinary; vaper; vaping; vapor

ABSTRACT – CORE 003: Biomarkers and Product Evaluation Core The goal of the Biomarkers and Product Evaluation Core is to facilitate the research proposed in Project MARVEL by providing data on biomarkers of exposure and biological effects as well as to characterize commonly used vaping products. These data will allow individual projects to achieve their Specific Aims. The measurement of toxicant and carcinogen metabolites in body fluids of people who use tobacco products is the accepted method for objective assessment of exposure to these products. Total nicotine equivalents (TNE), the sum of nicotine and six nicotine metabolites accounts for >85% of the nicotine dose, is a well-established biomarker of nicotine exposure. The primary pathway of nicotine metabolism is cytochrome P450 2A6 (CYP2A6)-catalyzed C-oxidation, which leads to the formation of cotinine. Cotinine is further metabolized, also by CYP2A6, to 3'-hydroxycotinine. The ratio of 3'-hydroxycotinine to cotinine in plasma or saliva (referred to as the NMR) is an excellent phenotypic measure of CYP2A6 activity, and may be used to characterize individual differences in nicotine metabolism. Urinary concentrations of the acrylonitrile mercapturic acid, 2-cyanoethyl- mercapturic acid (CEMA) is from 100 to more than 400 times higher in smokers compared to non-smokers and can be used to distinguish combustible from non-combustible tobacco use with sensitivity and specificity >99%. The mercapturic acids of acrolein, crotonaldehyde, and benzene, 3-hydroxypropyl-mercapturic acid (3HPMA), 3-hydroxy-1-methylpropylmercpturic acid (HMPMA), S-phenylmercapturic acid (SPMA) can be used to quantify exposure to volatile toxicants in cigarette and e-cigarette users. Oxidative damage can be measured with urinary 8-iso-PGF2α, an F2-isoprostane and elevated PGE-M, a prostaglandin-E2 metabolite is a biomarker of inflammation. Vaping products may vary widely in their fluid constituents and generated aerosol. The Core will analyze saliva samples from Lab Study participants for cotinine and the NMR. Urine samples from participants attending lab-based assessments will be analyzed for TNE, mercapturic acids, 8-iso-PGF2α and .PGE-M. The Core will also determine e-liquid constituents and generated aerosol yield of the most abundantly used e-cigarettes among the participants of this study. The Specific Aims are to: 1) Characterize individual differences in nicotine metabolism and exposure in participants in the cohort study; 2) Quantify exposure to other constituents found in tobacco products and systemic indices of oxidative stress and inflammation in participants of the lab-based assessments; 3) Characterize toxic constituents in e-liquids and aerosol. The Core is housed at the University of Minnesota which provides state-of-the-art expertise and technology for the quantitation of these biomarkers, and the constituents of e-cigarettes. The University of Minnesota is widely recognized as one of the leading academic centers for this research. Objective verification of product characteristics, user exposure, and biological effects is a critically important component of robust research on the health effects of tobacco products.

摘要 - 核心003：生物标志物和产品评估核心 生物标志物和产品评估核心的目的是促进项目中提出的研究 通过提供有关暴露和生物学效果的生物标志物的数据，并表征 常用的蒸发产品。这些数据将允许各个项目实现其特定目标。这 使用烟草产品的人体液中毒物和致癌代谢产物的测量是 可接受的方法评估这些产品的接触。总尼古丁等效物（tne）， 尼古丁和六个尼古丁代谢产物的总和占尼古丁剂量的85％，是一个公认的 尼古丁暴露的生物标志物。尼古丁代谢的主要途径是细胞色素P450 2A6 （CYP2A6） - 催化的C-氧化，导致可替宁的形成。可替宁也进一步代谢 由CYP2A6到3'-羟基霉素。血浆或唾液中3'-羟基霉素与可替宁的比率（称为 NMR）是CYP2A6活性的出色表型量度，可用于表征个体 尼古丁代谢的差异。丙烯酸硫酸硫酸的尿液浓度，2-氰基乙基 与非吸烟者相比 可以用来区分混合与非可燃烟草使用的敏感性和特异性 > 99％。丙烯醛，克罗托醛醛和苯的硫酸，3-羟基丙基 - 羟基苯甲酸 （3HPMA），3-羟基-1-甲基丙基丙酸（HMPMA），可以使用S-苯基 - 苯甲酸（SPMA） 量化在香烟和电子烟使用者中对挥发性有毒物质的暴露。氧化损伤可能是 Prostaglandin-e2代谢产物用尿液8-ISO-PGF2α，F2-异丙烷和升高的PGE-M测量 炎症的生物标志物。蒸气产物的液体构成并产生的气溶胶可能差异很大。 核心将分析来自Lab研究参与者的唾液样本和NMR。尿液样品 将分析参加基于实验室评估的参与者的胃酸，8-ISO-PGF2α 和.pge-m。核心还将确定最多的电子液体构成并产生的气溶胶产量 这项研究的参与者中几乎完全使用了电子烟。具体目的是：1）表征 队列研究中参与者的尼古丁代谢和暴露的个体差异； 2）量化 暴露于烟草产物中发现的其他成分以及氧化应激的系统指数和 基于实验室评估的参与者的炎症； 3）在电子液体中表征有毒构成和 气雾剂。该核心位于明尼苏达大学，该大学提供最先进的专业知识和 定量这些生物标志物的技术以及电子烟的构成。大学 明尼苏达州被广泛认为是这项研究的主要学术中心之一。客观验证 产品特性，用户曝光和生物学效应是鲁棒的重要组成部分 研究烟草产品的健康影响。