Core 3 - Biomarkers and Product Evaluation

摘要-CORE 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标是促进项目中提出的研究 Marvel通过提供暴露和生物效应的生物标记物数据以及表征 常用的蒸发产品。这些数据将使个别项目能够实现其特定目标。这个 使用烟草产品的人的体液中有毒和致癌代谢物的测量是 客观评估接触这些产品的公认方法。总尼古丁当量(TNE)， 尼古丁和六种尼古丁代谢物的总和占尼古丁剂量的85%，这是一个公认的 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。可替宁也会进一步代谢 由CYP2A6转化为3‘-羟基可替宁。血浆或唾液中3‘-羟基可替宁与可替宁的比率(称为 核磁共振)是一种很好的CYP2A6活性的表型指标，可以用来表征个体 尼古丁代谢的差异。2-氰乙基-2-氰乙基丙烯腈的尿液浓度 与非吸烟者相比，吸烟者体内的硫代尿酸(CEMA)含量高出100到400多倍 可用于区分可燃和非可燃烟草用途，具有敏感性和特异性 &gt；99%。丙烯醛、巴豆醛和苯基3-羟丙基-硫代尿酸的硫代尿酸 可以使用(3HPMA)、3-羟基-1-甲基丙基硫代尿酸(HMPMA)、S-苯硫代尿酸(SPMA) 量化香烟和电子烟使用者接触挥发性毒物的情况。氧化损伤可以是 测定尿8-iso-PGF_2α、F_2-异前列腺素E_2和升高的PGE-M，前列腺素E_2代谢物 炎症的生物标志物。蒸发产品的流体成分和产生的气溶胶可能有很大的不同。 Core将分析实验室研究参与者的唾液样本，以检测可替宁和核磁共振。尿样 将对参加实验室评估的参与者进行TNE、硫代尿酸、8-iso-PGF2α的分析 和.PGE-M的核心还将决定电子液体的成分和产生的气溶胶产量最多 在这项研究的参与者中，大量使用电子烟。具体目的是：1)描述 队列研究参与者尼古丁代谢和暴露的个体差异；2)量化 接触烟草产品中发现的其他成分和全身氧化应激指数和 以实验室为基础的评估参与者的炎症；3)表征电子液体和 气雾剂。核心位于明尼苏达大学，该大学提供最先进的专业知识和 这些生物标志物的量化技术以及电子烟的成分。伊利诺伊大学 明尼苏达州被广泛认为是这项研究的领先学术中心之一。客观验证 产品特性、用户暴露和生物效应是健壮的一个至关重要的组成部分 烟草产品对健康影响的研究。

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.