Core B: Biomarker and Constituent Core

摘要 生物标志物和成分核心(核心B)将对#年烟雾中的烟草成分进行分析。 商业和研究香烟，以及用于个别项目提出的研究中的电子烟， 并将分析从这些产品的用户那里收集的生物样本中的一组生物标记物。这些 分析将能够评估移除过滤器通风对公共健康的影响，如 这个节目。核心将采用基于标准化方法的成熟可靠的协议，以 烟草成分和生物标志物的分析，并将应用一些最新开发的创新 香烟烟雾和新型生物标志物的分析方法。对于产品分析，烟雾 将对商业和研究卷烟进行尼古丁和一系列关键有毒物质和致癌物质的分析 (烟草特有的N-亚硝胺、多环芳香烃和挥发性有机化合物)、过滤器 将测定通风量等卷烟物理参数，并对其组成进行差异分析 将评估通风和非通风香烟在不同烟雾颗粒上的分布。 研究参与者吸过的香烟中用过的滤嘴也将被分析以与口腔水平相关联 吸烟地形测量、生物标记物水平和/或感官知觉的成分暴露。这个 CORE还将产生香烟烟雾和电子烟气雾剂提取物，用于动物行为 其中一个项目中提出的研究，并将分析尼古丁和其他可能有助于 烟草产品的滥用责任，如次要生物碱、β-Caroline和醛。生物标记物 核心B将分析的特定烟雾成分包括总尼古丁当量的尿液水平 (尼古丁摄入量)，4-(甲基亚硝基)-1-(3-吡啶)-1-丁醇(NNAL)及其N-和O-葡萄糖醛酸苷 (接触烟草特有的肺癌物质NNK)、烟草特有的口腔和食道致癌物质N‘- 亚硝基烟碱(NNN)及其N-葡萄糖醛酸苷、菲四醇和3-羟基菲(暴露) 对具有代表性的多环芳烃(菲)和硫代尿酸的作用和代谢 酸(暴露于丙烯醛和巴豆醛)和DNA加合物N6-羟甲基脱氧腺苷和 N-亚乙叉-脱氧鸟苷分别来源于甲醛和乙醛。肺和全身 炎症过程将通过分析炎症细胞计数、细胞因子和基因来评估。 支气管镜检查标本中8-oxo-dg和8-oxo-da在白细胞DNA中的表达谱，以及pGEM和8-iso-dA 尿PGF_2α。此外，非靶向代谢组学将用于分析尿液和 用支气管肺泡灌洗液识别新的生物标志物图谱以区分暴露与通风和 不通风的香烟。该中心的工作人员在临床试验和量化方面拥有丰富的经验 烟草成分和生物标志物，并率先开发了许多方法学，将 在此核心中使用。烟草成分暴露的准确、稳健和统一的衡量标准的可用性 以及本核心中建议的这些暴露所造成的影响对研究的进行至关重要 由个别项目提出，并为这一计划的全面成功而努力。

ABSTRACT The Biomarker and Constituent Core (Core B) will carry out analyses of tobacco constituents in the smoke of commercial and research cigarettes, as well as in e-cigarettes, used in studies proposed by individual projects, and will analyze a panel of biomarkers in biological samples collected from users of these products. These analyses will enable the assessment of the public health impact of removing filter ventilation, as proposed in this program. The Core will employ well-established robust protocols based on standardized methodologies for the analyses of tobacco constituents and biomarkers, and will also apply some recently developed innovative methodologies for the analysis of cigarette smoke and novel biomarkers. For product analyses, smoke of commercial and research cigarettes will be analyzed for nicotine and a range of key toxicants and carcinogens (tobacco-specific N-nitrosamines, polycyclic aromatic hydrocarbons, and volatile organic compounds), filter ventilation and other cigarette physical parameters will be determined, and the differences in constituent distribution across various smoke particle sizes from ventilated and non-ventilated cigarettes will be assessed. Spent filters from cigarettes smoked by study participants will be also analyzed to correlate mouth-level constituent exposures with smoking topography measures, biomarker levels, and/or sensory perceptions. The Core will also generate cigarette smoke and e-cigarette aerosol extracts for the use in the animal behavioral studies proposed in one of the projects, and will analyze nicotine and other constituents that may contribute to abuse liability of tobacco products, such as minor alkaloids, β-carbolines, and aldehydes. Biomarkers of specific smoke constituents to be analyzed by Core B include urinary levels of total nicotine equivalents (nicotine intake), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its N- and O-glucuronides (exposure to tobacco-specific lung carcinogen NNK), the tobacco specific oral and esophageal carcinogen N′- nitrosonornicotine (NNN) and its N-glucuronide, phenanthrene tetraol and 3-hydroxy phenanthrene (exposure to and metabolism of the representative polycyclic aromatic hydrocarbon phenanthrene), and mercapturic acids (exposure to acrolein and crotonaldehyde), and DNA adducts N6-hydroxymethyl-deoxyadenosine and N2-ethylidene-deoxyguanosine derived from formaldehyde and acetaldehyde, respectively. Lung and systemic inflammatory processes will be assessed by analyzing inflammatory cell counts, cytokines, and gene expression profiles in bronchoscopy samples, 8-oxo-dG and 8-oxo-dA in leukocyte DNA, and PGEM and 8-iso- PGF2α in urine. In addition, untargeted metabolomics will be employed for the analysis of urine and bronchoalveolar lavage fluids to identify novel biomarker profiles distinguishing exposures from ventilated and non-ventilated cigarettes. Personnel in this Core have extensive experience in clinical trials and quantitation tobacco constituents and biomarkers, and were the first to develop many of the methodologies that will be used in this Core. Availability of the accurate, robust, and uniform measures of tobacco constituent exposures and of the effects caused by these exposures, as proposed in this Core, is critical for the conduct of studies proposed by individual projects and for the overall success of this program.