1,3-Butadiene (BD) is a known human carcinogen found in cigarette smoke, automobile exhaust, and urban air. Workers occupationally exposed to BD in the workplace have an increased incidence of leukemia and lymphoma. BD undergoes cytochrome P450-mediated metabolic activation to 3,4-epoxy-1-butene (EB), 1,2,3,4-diepoxybutane (DEB) and 1,2-dihydroxy-3,4-epoxybutane (EBD), which form covalent adducts with DNA. We have previously reported a quantitative nanoLC/ESI+-HRMS3 method for urinary N7-(1-hydroxy-3-buten-2-yl) guanine (EB-GII) adducts as a mechanism-based biomarker of BD exposure. In the present study, the method was updated to include high throughput 96-well solid phase extraction (SPE) and employed to establish urinary EB-GII biomarker stability and association with smoking. Urinary EB-GII levels were measured bimonthly for 1 year in 19 smokers to determine whether single adduct measurement provides reliable levels of EB-GII in an individual smoker. In addition, association of EB-GII with smoking was studied in 17 individuals participating in a smoking cessation program. EB-GII levels decreased 34% upon smoking cessation, indicating that it is associated with smoking status, but may also originate from sources other than exposure to cigarette smoke.

中文翻译：

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人体尿 N7-(1-hydroxy-3-buten-2-yl) 鸟嘌呤加合物：时间稳​​定性和与吸烟的关联。

1,3-丁二烯 (BD) 是一种已知的人类致癌物，存在于香烟烟雾、汽车尾气和城市空气中。在工作场所职业性接触 BD 的工人患白血病和淋巴瘤的几率增加。BD 经历细胞色素 P450 介导的代谢激活，生成 3,4-环氧-1-丁烯 (EB)、1,2,3,4-二环氧丁烷 (DEB) 和 1,2-二羟基-3,4-环氧丁烷 (EBD)，与 DNA 形成共价加合物。我们之前报道了一种定量 nanoLC/ESI+-HRMS3 方法，用于尿 N7-(1-hydroxy-3-buten-2-yl) 鸟嘌呤 (EB-GII) 加合物作为 BD 暴露的基于机制的生物标志物。在本研究中，该方法已更新为包括高通量 96 孔固相萃取 (SPE)，并用于确定尿液 EB-GII 生物标志物的稳定性和与吸烟的关联。对 19 名吸烟者的尿液 EB-GII 水平进行为期 1 年的双月测量，以确定单一加合物测量是否能提供个体吸烟者可靠的 EB-GII 水平。此外，在 17 名参与戒烟计划的个体中研究了 EB-GII 与吸烟的关联。EB-GII 水平在戒烟后下降了 34%，这表明它与吸烟状况有关，但也可能源于接触香烟烟雾以外的其他来源。