Masonic Cancer Center, University of Minnesota, Minneapolis, MN.
Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN.
Mutagenesis. 2020 Feb 13;35(1):19-26. doi: 10.1093/mutage/gez030.
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.
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。职业性接触 BD 的工人中，白血病和淋巴瘤的发病率增加。BD 通过细胞色素 P450 介导的代谢激活为 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），这些物质与 DNA 形成共价加合物。我们之前报道了一种用于尿液 N7-（1-羟基-3-丁烯-2-基）鸟嘌呤（EB-GII）加合物的定量纳升液相色谱/电喷雾+高分辨率质谱（nanoLC/ESI+-HRMS）方法，作为 BD 暴露的基于机制的生物标志物。在本研究中，该方法进行了更新，包括高通量 96 孔固相萃取（SPE），并用于建立尿液 EB-GII 生物标志物的稳定性及其与吸烟的关系。对 19 名吸烟者进行了为期 1 年的双月尿液 EB-GII 水平测量，以确定单次加合物测量是否能提供个体吸烟者 EB-GII 的可靠水平。此外，还在 17 名参加戒烟计划的个体中研究了 EB-GII 与吸烟的关系。戒烟后 EB-GII 水平下降了 34%，表明它与吸烟状况有关，但也可能源自除香烟烟雾暴露以外的其他来源。
