UNIVERSITY OF LOUISVILLE NIEHS CENTER DEVELOPMENTAL GRAN

已经协调了一项前瞻性的工业卫生监督计划， 卡洛H。Tamburro，医学博士，M.P.H.职业毒理学部， 联合路易斯维尔医学院在过去的20年。 这个程序 提供了一套独特的人类医疗数据，工作接触历史， 组织/血清样本，适用于短期和长期分析 有毒化学品暴露的生物标志物。 这个职业的暴露 一直在监测人口对工业化学品的接触情况， 经过12-40年的验证。 在大路易斯维尔地区， 大量医疗上不应得和经济上处于不利地位的人口 居住在工业区附近，他们的病史可以 与工业同行相比。 这些不利的住宅 可以通过拟议的生物标志物计划监测人群， 他们的身体负担相对于产业工人和他们的同龄人。 该中心的医疗监督方面将提供必要的 人类医疗数据、工作经历和组织，以建立相关性 在建议的短期和长期生物标志物与实际的 与这些化学废水有关的疾病过程 工业用地。 获得的数据将使更可靠的因果关系 与人口和发展之间的联系， 验证生物标志物的敏感性和特异性。 的主题 L中心的U将专注于使用生物化学，化学， 确定人群暴露的分子生物学生物标志物 并评估这些受试者随后的健康风险， 预防和治疗方式。 已选定五个试点项目，重点是健康 对路易斯维尔工业和居民的监测 接触丙烯腈、氯乙烯和各种金属 已知毒理学重要性的催化剂。 项目1（坦布罗/鲁尼） 涉及医疗数据和暴露的收集、存储和分析 历史和收集的人体组织样本进行分析， 以下项目的生物标志物计划。 项目2（奔驰/Nerland） 将研究丙烯腈和氯乙烯在大鼠体内的代谢， 人肝细胞。 项目3（Hurst/Myers）将评估以下生物标志物： 涉及血红蛋白和DNA加合物的中等暴露持续时间 丙烯腈。 项目4（Brennan/Prough）将进行短期评估， 丙烯腈，氯乙烯， 和金属催化剂暴露，即诱导和持久性 外源化合物代谢的几种酶的表达。 项目 5（Geoghegan/Myers/Wong）将评价长期生物标志物，即 p53肿瘤抑制基因突变已知与 人类接触丙烯腈导致的血管瘤。

A prospective industrial health surveillance program has been coordinated by Carlo H. Tamburro, M.D., M.P.H., Division of Occupational Toxicology, U. Louisville School of Medicine for the past 20 years. This program provides a unique set of human medical data, work-exposure histories and tissue/serum samples suitable for analysis of short-and long-term biomarkers of toxic chemical exposure. The exposure of this occupational population to industrial chemicals has been continuously monitored and verified for periods of 12-40 years. In the Greater Louisville area, a large medically undeserved and economically-disadvantaged population resides adjacent to the industrial sites and their medical histories can be compared to industrial cohorts. These disadvantage residential populations can be monitored by the proposed biomarker program to assess their body burden relative to the industrial workers and their cohorts. The medical surveillance aspects of this Center will provide essential human medical data, work histories and tissue to develop correlations between the proposed short and long term-biomarkers with the actual disease processes associated with the chemical effluent of these industrial sites. The data obtained would allow more reliable causal linkages to be made or disprove with regard to the populations and validate the biomarkers sensitivity and specificity. The Theme for the U of L Center will focus on the use of biochemical, chemical, and molecular biological biomarkers to define exposure in human populations and to assess in these subjects subsequent health risk requiring preventive and therapeutic modalities. Five Pilot Projects have been selected which would focus on the health surveillance of industrial and residential populations in Louisville exposures to acrylonitrile, vinyl chloride, and a variety of metal catalysts of known toxicological importance. Project 1 (Tamburro/Looney) involves collection, storage, and analysis of medical data & exposure histories and collection of human tissue samples to be analyzed in the biomarker program of the following Projects. Project 2 (Benz/Nerland) will study metabolism of acrylonitrile and vinyl chloride in rat and human hepatocytes. Project 3 (Hurst/Myers) will evaluated biomarkers of intermediate duration of exposure involving hemoglobin and DNA adducts of acrylonitrile. Project 4 (Brennan/Prough) will evaluated short and potentially intermediate-term markers of acrylonitrile, vinyl chloride, and metal catalyst exposure, namely induction and persistence of expression of several enzymes of foreign compound metabolism. Project 5 (Geoghegan/Myers/Wong) will evaluated a long term biomarker, namely mutation of p53 tumor suppressor gene known to be associated with angiosarcomas derived from acrylonitrile exposure in humans.