BIOMARKERS OF STYRENE OXIDE

氧化苯乙烯的生物标志物

• 批准号: 2113527
• 负责人: Stephen M Rappaport
• 金额: $ 39.33万
• 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/2113527
• 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， 苯乙烯-7,8-氧化物（SO），由苯乙烯在反应过程中的反应产生 增强塑料的生产，导致SO显着增加 生物标志物 [SO 与 DNA 和血清白蛋白以及姐妹染色单体的加合物 交流]在工人中。这一发现非常引人注目，因为同时暴露于 苯乙烯含量为 SO 的 400 倍时，仅产生轻微的（如果有的话） 尽管转化了这些相同的 SO-生物标志物 几乎所有的苯乙烯都通过人类肝脏转化为SO。拟议的研究是 旨在确定吸入苯乙烯和 SO 至强化作业人员血液中 SO 的综合剂量 塑料工业。为了实现这个目标，我们将招募100名工人 强化塑料行业的 17 家工厂。我们将测量 每个工人在一次工作中两次在空气中接触苯乙烯和二氧化硫 年。每次调查期间还将收集血液样本，以便我们 可以测量血液中苯乙烯和SO的浓度以及 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 和 SO 到血液中 SO 的综合剂量，同时也解决了 以下问题：1）验证使用蛋白质加合物来估计 血液中 SO 的积分剂量，2) 比较 SO 的 DNA 加合物 通过高分辨率质谱法测量（鸟嘌呤的 N-7 加合物） 与通过 32P-后标记（鸟嘌呤的 N2 加合物）测量的结果，以及 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得到实现。第一的， 我们将确定与配方和使用相关的因素如何 增强塑料会影响苯乙烯和二氧化硫的暴露。这将是 通过在每次调查期间收集有关以下方面的信息来完成 树脂配方以及各个工人的工作和任务 然后确定这些因素对暴露的贡献 苯乙烯和SO。其次，我们将确定SO本身是否是源头 使用超痕量技术测定人血液中 SO 的背景加合物 100 名无职业接触者血液中 SO 分析 苯乙烯或SO。蛋白质和 DNA 加合物也将在 这些人使我们能够将背景加合物水平与那些人进行比较 血液中的SO。第三，我们将确定工人是否具有相对 低水平的 SO-DNA 加合物显示 DNA 修复的更高表达 系统，N-甲基嘌呤-DNA糖基化酶，比工人相对高 SO-DNA 加合物的水平。