Core B: Biomarker and Constituent Core

核心 B：生物标志物和核心成分

• 批准号: 9358860
• 负责人: Irina Stepanov
• 金额: $ 39.95万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9358860
• 关键词: 1-Butanol; 2-butenal; Acetaldehyde; Acetylcysteine; Acrolein; Aerosols; Aldehydes; Alkaloids; Animal Experiments; Animal Model; Animals; Aromatic Polycyclic Hydrocarbons; Behavioral; Beta Carbolines; Biological; Biological Assay; Biological Markers; Bronchoalveolar Lavage Fluid; Bronchoscopy; Carcinogens; Cell Count; Cells; Characteristics; Chemicals; Cigarette; Clinical Trials; Cotinine; Cytokine Gene; DNA; DNA Adducts; Data; Data Analytics; Deoxyadenosines; Deoxyguanosine; Development; Electronic cigarette; Environmental air flow; Equipment; Esophageal; Excision; Exposure to; Formaldehyde; Gene Expression Profiling; Glucuronides; Goals; Human; Human Resources; Impact evaluation; Individual; Inflammation; Inflammatory; Intake; Investigation; Laboratories; Leukocytes; Link; Liquid substance; Location; Lung; Malignant neoplasm of lung; Measures; Metabolism; Methodology; Methods; Minnesota; Minor; Molecular Profiling; N' -nitrosonornicotine; Nicotine; Nitrosamines; Ohio; Oral; Oral cavity; Outcome; Oxidative Stress; Participant; Particle Size; Perception; Plasma; Process; Protocols documentation; Public Health; Rattus; Recruitment Activity; Research; Research Personnel; Sampling; Sensory; Services; Smoke; Smoker; Smoking; Smoking Behavior; Source; Standardization; Techniques; Tobacco; Toxic effect; Toxicology; Translating; Universities; Urine; base; behavioral economics; behavioral health; behavioral study; biomarker panel; cancer risk; carcinogenicity; cigarette smoking; cytokine; experience; innovation; insight; metabolomics; multidisciplinary; novel marker; novel strategies; phenanthrene; programs; response; specific biomarkers; success; tool; toxicant; urinary; volatile organic compound

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.

摘要 生物标志物和成分核心（核心B）将对烟草烟雾中的烟草成分进行分析， 商业和研究香烟，以及电子香烟，用于个别项目提出的研究， 并将分析从这些产品的用户收集的生物样本中的一组生物标志物。这些 分析将使公众健康的影响进行评估，删除过滤器通风，建议在 这个戒酒会这核心方案将采用基于标准化方法的成熟可靠的协议， 烟草成分和生物标志物的分析，并将应用一些最近开发的创新 分析香烟烟雾和新型生物标志物的方法。对于产品分析， 将对商业和研究香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、多环芳烃和挥发性有机化合物），过滤器 通风和其他卷烟物理参数将被确定， 将评估通风和非通风香烟的各种烟雾颗粒尺寸的分布。 还将分析研究参与者吸烟的废过滤嘴， 成分暴露与吸烟地形测量、生物标志物水平和/或感官知觉。的 核心还将产生香烟烟雾和电子烟气溶胶提取物，用于动物行为研究。 其中一个项目提出的研究，并将分析尼古丁和其他成分，可能有助于 烟草制品的滥用倾向，如次要生物碱、β-咔啉和醛。的生物标志物 由核心B分析的特定烟雾成分包括总尼古丁当量的尿水平 （尼古丁摄入量）、4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁醇（NNAL）及其N-和O-葡萄糖醛酸苷 （暴露于烟草特异性肺致癌物NNK），烟草特异性口腔和食管致癌物N′- 亚硝基去甲烟碱（NNN）及其N-葡萄糖醛酸苷、菲四醇和3-羟基菲（暴露 和代谢的代表性多环芳烃菲），和巯基尿酸 酸（暴露于丙烯醛和巴豆醛）和DNA加合物N6-羟甲基-脱氧腺苷， N2-亚乙基-脱氧鸟苷分别来源于甲醛和乙醛。肺部和全身 炎症过程将通过分析炎症细胞计数、细胞因子和基因表达来评估。 支气管镜检查样本中的表达谱、白细胞DNA中的8-氧代-dG和8-氧代-dA以及PGEM和8-异- 尿PGF 2 α。此外，非靶向代谢组学将用于尿液分析， 支气管肺泡灌洗液，以确定区分通气和 不通风的香烟。该核心的工作人员在临床试验和定量方面具有丰富的经验 烟草成分和生物标志物，并率先开发了许多方法， 在这个核心中使用。烟草成分暴露的准确、可靠和统一测量的可用性 以及本核心中提出的这些照射所造成的影响，对于开展研究至关重要。 为项目的整体成功而努力。