Core B - The Clinical and Biomarkers Core

摘要 临床和生物标记物核心对于本计划项目更新提案中的研究至关重要。《核心》 将招募吸烟者收集生物样本，并将对烟草成分生物标志物进行分析。 中心收集的生物样本将用于评估和比较烟草的生物标志物。 日裔美国人、白人和夏威夷原住民在项目2、3和4中的暴露情况。 核心分析包括总尼古丁当量(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-葡萄糖醛酸化物(暴露于烟草特有的肺癌致癌物质NNK)， 菲四醇和3-羟基菲(接触和代谢代表 多环芳烃菲)、硫代糖酸(暴露于丙烯醛、巴豆醛和 环氧丙烷)、尿镉以及来自氧化的尿生物标志物和DNA加合物 压力和炎症。这项测量将对总共6084名受试者的样本进行，其中 这些样本中的一些只被分析为生物标志物的子集。这些受试者的样本将 要么从多种族队列的现有生物抵抗力获得，要么从吸烟者那里获得 被这个核心招募。除了尿镉以外，所有的分析都是基于稳定同位素稀释量。 在准确度和精密度方面，所有这些都经过了分析验证。本公司的人员 CORE在尿液烟草生物标志物和DNA的临床试验和定量方面拥有丰富的经验 加合物，并是第一个开发了许多方法，将用于该计划的项目赠款。这个 所有项目都将使用该核心产生的生物样本和生物标记结果。

ABSTRACT The Clinical and Biomarkers Core is critical for the studies in this program project renewal proposal. The Core will recruit smokers to collect biological samples and will carry out analyses of tobacco constituent biomarkers. The biological samples collected by the Core will be used to evaluate and compare biomarkers of tobacco exposure across Japanese Americans, Whites, and Native Hawaiians in Projects 2, 3, and 4. Biomarkers to be analyzed by the Core include 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), phenanthrene tetraol and 3-hydroxy phenanthrene (exposure to and metabolism of the representative polycyclic aromatic hydrocarbon phenanthrene), mercapturic acids (exposure to acrolein, crotonaldehyde, and propylene oxide), urinary cadmium, as well as urinary biomarkers and DNA adducts derived from oxidative stress and inflammation. The measurements will be carried out on samples from a total of 6,084 subjects, with some of these samples being analyzed for only a subset of biomarkers. The samples from these subjects will either be procured from the existing bioresposity of the Multiethnic Cohort or obtained from smokers who are recruited by this Core. All assays, except for urinary cadmium, are based on stable-isotope dilution mass spectrometry and all have been analytically validated with respect to accuracy and precision. Personnel in this Core have extensive experience in clinical trials and quantitation of urinary tobacco biomarkers and DNA adducts, and were the first to develop many of the methods that will be used in this program project grant. The biological samples and biomarker results generated by this Core will be used by all projects.