COLLABORATIVE STUDY OF 1,3 BUTADIENE BIOMARKERS

1，3-丁二烯（BD）是由汽油释放的常见空气污染物， 香烟烟雾和汽车尾气。 在人类中，BD被氧化 通过P450酶（CYP 2 E1，2 E1）转化为环氧丁烯、环氧丁二醇和 二环氧丁烷（？），其被多晶型环氧化物水解酶失活 （EH）。 BD被归类为可疑的人类致癌物。 BD是 酶的激活和失活，所以基因上 预期敏感性的差异。 三种生物标志物 显示出估计环氧丁烯内部剂量的希望， 环氧丁二醇;血红蛋白N-末端缬氨酸加合物，淋巴细胞7- 烷基鸟嘌呤DNA加合物，以及 丁烯二醇建议多中心合作， 这些剂量生物标志物中每一种的剂量-剂量关系。 这 关系由生物标志物的背景水平，斜率， 精度、偏差和干扰。 这种关系受到 个体的2 E1表型、EH基因型和生活方式因素， 将被评估。 将从男性中抽取80例受试者 生产丁二烯胶乳及相关产品的台湾石化工人 在10个大型工厂生产产品（共250名工人）。 受试者将 选择20例受试者的4个激活/失活亚组， 2 E1激活速率快或慢，正常或变异型EH 基因型80例对照，年龄和代谢与 暴露的，将从当地未暴露的工人中抽取。 初步 抽样显示两种类型的暴露：高强度（大于100 ppm平均值，持续2-3小时）在罐清洗期间，以及长期低液位 （中位数0.5-2 ppm全偏移）， 同时接触苯乙烯或丙烯腈。20个坦克清洁工 将提供关于高暴露反应的数据。 长期暴露（5 将对80名操作员进行监测。 血液和尿液样本 将在给药前、给药3周后和给药5周后采集样本，以确定 生物标志物水平及其在测量暴露期间的变化。 将通过回归分析暴露量-生物标志物关系 技术来观察新陈代谢和个人因素的影响。 模拟显示，该策略估计的斜率为q20%（95 百分之CI）的氧化失活亚组20，并有80 检测q10%差异的功效百分比（p小于0.05） 子组之间的斜率。 将比较生物标志物的背景 水平、偏差和灵敏度，以及样本采集的难易程度， 分析.

1,3-butadiene (BD) is a common air pollutant released by gasoline, cigarette smoke, and automobile emissions. In humans, BD is oxidized by P450 enzymes (CYP2E1, 2E1) to epoxybutene, epoxybutanediol and diepoxybutane(?), which are deactivated by polymorphic epoxide hydrolase (EH). BD is classified as a suspect human carcinogen. BD is enzymatically activated and deactivated, so genetically based differences in susceptibility are expected. Three types of biomarkers show promise for estimating internal dose of epoxybutene and epoxybutanediol; hemoglobin N-terminal valine adducts, lymphocyte 7- alkylguanine DNA adducts, and the urinary mercapturic acid of butenediol. A multicenter collaboration is proposed to quantity exposure-dose relationships for each of these biomarkers of dose. This relationship is defined by a biomarker's background levels, slope, precision, biases and interferences. This relationship is affected by an individual's 2E1 phenotype, EH genotype, and lifestyle factors, which will be assessed. Eighty (80) subjects will be drawn from male Taiwanese petrochemical workers producing butadiene latex and related products at 10 large plants (250 workers total). Subjects will be selected as 4 activation/deactivation subgroups of 20 subjects with either fast or slow 2E1 activation rates, and normal or variant EH genotypes. Eighty (80) controls, age and metabolism matched to the exposed, will be drawn from local unexposed workers. Preliminary sampling showed two types of exposures: high intensity (greater than 100 ppm average for 2-3 hr.) during tank cleaning, and long-term low level (medians 0.5-2 ppm full shift) during normal operations, and little concurrent exposure to styrene or acrylonitrite. Twenty tank cleaners will provide data on high exposure responses. Long-term exposures (5 wks) will be monitored for the 80 operators. Blood and urine samples will be collected before, after 3 wks, and after 5 wks to determine biomarker levels and their changes during the measured exposure. Exposure-biomarkers relationships will be analyzed by regression techniques to see effects of metabolism and personal factors. Simulations showed the strategy estimated slopes to q20 percent (95 percent CI) for an oxidation-deactivation subgroup of 20, and had 80 percent power (p less than 0.05) to detect a q10 percent difference in slopes among subgroups. Biomarkers will be compared for background levels, biases and sensitivity, and ease of sample collection and analysis.