Urinary N7-(1-hydroxy-3-buten-2-yl) guanine adducts in humans: temporal stability and association with smoking
Urinary N7-(1-hydroxy-3-buten-2-yl) guanine adducts in humans: temporal stability and association with smoking
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DOI：
10.1093/mutage/gez030
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发表时间：
2020-01-01
期刊：
影响因子：
2.7
通讯作者：
Tretyakova, Natalia
中科院分区：
文献类型：
--
作者：
Krueger, Caitlin C. Jokipii;Madugundu, Guru;Tretyakova, Natalia
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。在工作场所接触双相障碍的工人患白血病和淋巴瘤的几率增加。BD经过细胞色素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）加合物的定量纳米olc /ESI+- hrms方法，该方法可作为BD暴露的基于机制的生物标志物。在本研究中，该方法更新为包括高通量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名吸烟者进行为期1年的尿液EB-GII水平测量，以确定单一加合物测量是否能提供可靠的单个吸烟者EB-GII水平。此外，EB-GII与吸烟的关系在17名参与戒烟计划的个人中进行了研究。戒烟后EB-GII水平下降了34%，这表明它与吸烟状况有关，但也可能源于吸烟以外的其他来源。
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.