BIOMARKERS OF STYRENE OXIDE

氧化苯乙烯的生物标志物

• 批准号: 2769834
• 负责人: Stephen M Rappaport
• 金额: $ 36.12万
• 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 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2769834
• 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，暴露于致癌物质， 苯乙烯-7，8-氧化物（SO），其由苯乙烯在聚合过程中的反应产生。 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 在工人中的交流。这一发现是值得注意的，因为共同暴露于 苯乙烯的含量是SO的400倍，仅导致轻微的（如果有的话） 这些相同的SO-生物标志物的产生，尽管转化为 几乎所有的苯乙烯到SO的人的肝脏。拟定研究 旨在确定吸入的苯乙烯和 SO对钢筋工血中SO的累积剂量 塑料工业。为实现这一目标，我们将招聘100名工人 在强化塑料行业的17个工厂内。我们将测量 每个工人在一个工作日内两次接触苯乙烯和SO， 年此外，每次调查亦会抽取血液样本， 可以测量血液中苯乙烯和SO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 和SO到SO在血液中的综合剂量，但也要解决 以下问题：1）验证使用蛋白质加合物来估计 SO在血液中的累积剂量; 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32 P-后标记（鸟嘌呤的N2加合物）测量的那些，和3） 以确定SO的蛋白质和DNA加合物之间的关系。 还将追求调查的三个次要目标。第一、 我们将确定如何制定和使用相关的因素， 增强塑料影响苯乙烯和SO的暴露。这将是 通过在每次调查期间收集有关 树脂配方以及工人的工作和任务 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本身是否是来源 用超痕量技术测定人血中SO的背景加合物 100名非职业性接触者血中SO含量分析 苯乙烯或SO。蛋白质和DNA加合物也将在 这些人，使我们能够比较背景加合物水平与那些 在血液中。第三，我们将确定工人是否与相对 低水平的SO-DNA加合物显示DNA修复的更大表达 系统，N-甲基嘌呤-DNA糖基化酶，比工人相对较高 SO-DNA加合物的水平。

项目成果

Measurement of styrene-7,8-oxide and other oxidation products of styrene in air.

空气中苯乙烯-7,8-氧化物和苯乙烯的其他氧化产物的测量。

• DOI: 10.1039/a908976d
• 发表时间: 2000
• 期刊: Journal of environmental monitoring : JEM.
• 作者: Tornero-Velez,R;Waidyanatha,S;Echeverria,D;Rappaport,SM
• 通讯作者: Rappaport,SM

Physiological modeling of the relative contributions of styrene-7,8-oxide derived from direct inhalation and from styrene metabolism to the systemic dose in humans.

直接吸入和苯乙烯代谢产生的苯乙烯-7,8-氧化物对人体全身剂量的相对贡献的生理模型。

• DOI: 10.1093/toxsci/64.2.151
• 发表时间: 2001
• 期刊: Toxicological sciences : an official journal of the Society of Toxicology
• 作者: Tornero-Velez,R;Rappaport,SM
• 通讯作者: Rappaport,SM

Comparison of styrene-7,8-oxide adducts formed via reaction with cysteine, N-terminal valine and carboxylic acid residues in human, mouse and rat hemoglobin.

与人、小鼠和大鼠血红蛋白中的半胱氨酸、N 末端缬氨酸和羧酸残基反应形成的苯乙烯-7,8-氧化物加合物的比较。

• DOI: 10.1016/s0009-2797(97)00059-8
• 发表时间: 1997
• 期刊: Chemico-biological interactions
• 影响因子: 5.1
• 作者: Yeowell-O'Connell,K;Pauwels,W;Severi,M;Jin,Z;Walker,MR;Rappaport,SM;Veulemans,H
• 通讯作者: Veulemans,H

An investigation of factors contributing to styrene and styrene-7,8-oxide exposures in the reinforced-plastics industry.

对增强塑料行业中苯乙烯和苯乙烯-7,8-氧化物暴露影响因素的调查。

• 发表时间: 1999
• 期刊: The Annals of occupational hygiene.
• 作者: Nylander-French,LA;Kupper,LL;Rappaport,SM
• 通讯作者: Rappaport,SM

Determination of styrene and styrene-7,8-oxide in human blood by gas chromatography-mass spectrometry.

气相色谱-质谱法测定人血液中的苯乙烯和苯乙烯-7,8-氧化物。

• DOI: 10.1016/s0378-4347(01)00063-9
• 发表时间: 2001
• 期刊: Journal of chromatography. B, Biomedical sciences and applications
• 作者: Tornero-Velez,R;Waidyanatha,S;Pérez,HL;Osterman-Golkar,S;Echeverria,D;Rappaport,SM
• 通讯作者: Rappaport,SM