GENETIC SUSCEPTIBILITY AND OCCUPATIONAL HEALTH PROBLEMS

预防职业健康问题的努力受到限制， 缺乏可靠的生物标志物来预测暴露于 工作场所的有毒物质。 我们建议，继承某些 增加体内有毒化学物质负荷的多态性代谢基因 代谢物，使工人易患职业健康问题。 一组250名石油化工工人， 苯和谁以前被调查将被研究，以测试我们的 假说. 这些工人将被分为低、中、高三类 根据记录的苯暴露对健康的影响，对接触组进行评估。 来自这些工人的淋巴细胞将被基因分型，以遗传 不利的多态性基因，如CYP2D6的活性代谢物， 突变的过表达CYP2E1和GSTM1和GSTT1的无效基因型。 我们 预计工人患职业病的相对风险将 与特定基因型和暴露显著相关 苯的分类，并因酒精消费而加强， 吸烟。 将对基因分型工人的一个子集进行研究， 确定CYP2E1基因的表达（如体内 氯唑沙宗的代谢）将与 尿t，t-粘康酸浓度增加， 染色体畸变（通过荧光原位测定， 杂交技术）。 这项研究将使我们能够评估 采用新的方法来确定工作场所的危险， 个体工人，以改善风险评估过程，并帮助 指导职业健康问题预防决策。

Efforts to prevent occupational health problems have been limited by the lack of reliable biomarkers that predict health effects from exposure to toxicants at work sites. We propose that the inheritance of certain polymorphic metabolizing genes that increase body burden of toxic chemical metabolites, predisposes workers to develop occupational health problems. A group of 250 petrochemical workers who have significant exposure to benzene and who have previously been surveyed will be studied to test our hypothesis. These workers will be classified into low, medium and high exposure groups, according to documented benzene-exposure health effects. Lymphocytes from these workers will be genotyped for inheritance of unfavorable polymorphic genes such as active metabolizer for CYP2D6, mutated overexpressed CYP2E1 and null genotypes for GSTM1 and GSTT1. We anticipate that the workers' relative risk for occupational diseases will be significantly associated with specific genotypes and exposure classification for benzene and enhanced by alcohol consumption and cigarette smoking. A subset of the genotyped workers will be studied to determine if expression of the CYP2E1 gene (as indicated by in vivo metabolism of chlorzosazone) will be significantly correlated with increased urine t,t-muconic acid concentrations and with increased chromosome aberrations (as determined by the fluorescence-in-situ- hybridization technique). The study will allow us to evaluate the applicaton of a new approach to identify hazards at work sites on individual workers, to improve the risk assessment process and to help guide decision making on prevention of occupational health problems.