BIOMARKERS OF STYRENE OXIDE

氧化苯乙烯的生物标志物

• 批准号: 2517694
• 负责人: Stephen M Rappaport
• 金额: $ 34.32万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-30 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2517694
• 关键词: DNA damage; DNA repair; adduct; albumins; biomarker; blood chemistry; chemical carcinogen; environmental toxicology; guanine analog; hemoglobin; human tissue; mass spectrometry; occupational hazard; oxides; polystyrenes

Preliminary evidence is presented that exposures to the carcinogen, styrene-7,8-oxide (SO), which arise from reactions of styrene during the production of reinforced plastics, cause significant increases of SO biomarkers [adducts of SO with DNA and serum albumin and sister-chromatid exchanges] in workers. This finding is remarkable because coexposure to styrene at levels of 400 times those of SO results in only minor (if any) production of these same SO-biomarkers, despite the conversion of virtually all styrene to SO by the human liver. The proposed study is intended to determine the relative contributions of inhaled styrene and SO to the integrated dose of SO in the blood of workers in the reinforced plastics industry. To achieve this goal, we will recruit 100 workers within 17 facilities in the reinforced plastics industry. We will measure the airborne exposures of each worker to styrene and SO twice during one year. Blood samples will also be collected during each survey so that we can measure the Concentrations of styrene and SO in the blood as well as the levels of SO-adducts of albumin, Hb, and lymphocyte DNA. These data will not only allow us to determine the relative contributions of styrene and SO to the integrated dose of SO in the blood, but also to address the following issues: 1) to validate the use of protein adducts to estimate the integrated dose of SO in blood, 2) to compare DNA adducts of SO measured by high-resolution mass spectrometry (N-7 adducts of guanine) with those measured by 32P-postlabeling (N2 adducts of guanine), and 3) to determine the relationships among the protein and DNA adducts of SO. Three secondary goals of the investigation will also be pursued. First, we will determine how factors related to the formulation and use of reinforced plastics affect exposures to styrene and SO. This will be accomplished by gathering information during each survey regarding formulations of resins as well as the jobs and tasks of individual workers and then determining the contributions of these factors on exposure to styrene and SO. Second, we will determine whether SO per se is the source of background adducts of SO in human blood by employing ultratrace analyses of SO in the blood of 100 persons without occupational exposures to styrene or to SO. Protein and DNA adducts will also be measured in these persons to allow us to compare background adduct levels with those of SO in blood. Third, we will determine whether workers with relatively low levels of SO-DNA adducts show greater expression of the DNA repair system, N-methylpurine-DNA glycosylase, than workers with relatively high levels of SO-DNA adducts.

初步证据表明，接触致癌物质， 苯乙烯-7，8-氧化物(SO)，由苯乙烯在反应过程中产生 增强塑料的生产，导致SO显著增加 生物标志物[SO与DNA、血清白蛋白和姐妹染色单体的加合物 交流]在工人中。这一发现是值得注意的，因为共同暴露于 当苯乙烯的含量达到400倍时，只会产生少量的(如果有的话)。 生产这些相同的SO-生物标志物，尽管 几乎所有的苯乙烯都是由人体肝脏产生的。建议的研究是 旨在确定吸入的苯乙烯和 所以要给工人血液中的综合剂量的SO加强 塑料工业。为了实现这一目标，我们将招聘100名工人 在增强塑料行业的17家工厂内。我们将衡量 每名工人在一年内暴露在空气中的苯乙烯和两次 年。我们亦会在每次调查期间收集血液样本，以便我们 可以测量血液中的苯乙烯和二氧化硫的浓度 白蛋白、Hb和淋巴细胞DNA的SO加合物水平。这些数据 不仅能让我们确定苯乙烯的相对贡献率 并因此对血液中的综合剂量进行补充，也是为了解决 以下问题：1)验证使用蛋白质加合物来估计 血中SO的积分剂量，2)比较SO的DNA加合物 用高分辨率质谱仪(鸟嘌呤N-7加合物)测定 用~(32)P-后标记(鸟嘌呤的N_2加合物)测定，和3) 确定SO的蛋白质和DNA加合物之间的关系。 调查的三个次要目标也将被追求。第一, 我们将确定与制定和使用 强化塑料会影响对苯乙烯等的暴露。这将是 通过在每次调查期间收集有关以下方面的信息来实现 树脂配方以及个体工人的工作和任务 然后确定这些因素对暴露于 苯乙烯之类的。其次，我们将确定这样的本身是否是来源 利用超音速技术研究人血中硫化物的背景加合物 100例非职业性接触者血中硫化物分析 到苯乙烯或到这样的。蛋白质和DNA加合物也将在 这些人使我们能够比较背景加合物水平与 在鲜血中。第三，我们将确定工人是否具有相对 低水平的SO-DNA加合物表明DNA修复的表达更多 系统，N-甲基嘌呤-DNA糖基化酶，比工人具有相对较高的 SO-DNA加合物的水平。