GENETIC SUSCEPTIBILITY AND OCCUPATIONAL HEALTH PROBLEMS

预防职业健康问题的努力受到以下因素的限制 缺乏可靠的生物标志物来预测接触铅对健康的影响 工作场所的毒物。我们建议，某些遗产的继承 增加身体有毒化学物质负担的多态代谢基因 代谢物，使工人容易出现职业健康问题。 一组250名石化工人，他们有大量接触 苯和以前被调查过的人将被研究以测试我们的 假设。这些工人将被分成低、中、高三类 暴露组，根据文件记录的苯暴露对健康的影响。 这些工人的淋巴细胞将进行基因分型，以遗传 不利的多态基因，如CYP2D6的活性代谢物， 突变的GSTM1和GSTT1高表达的CYP2E1和零基因。我们 预计工人患职业病的相对风险将 与特定的基因类型和暴露显著相关 对苯进行分类，并通过酒精消费和 抽烟。将对一部分基因分型工人进行研究，以 确定CYP2E1基因的表达(如体内所示 氯唑沙宗的新陈代谢)将与 尿中t，t-Muconic酸浓度增加，并随着 染色体畸变率(由原位荧光测定) 杂交技术)。这项研究将使我们能够评估 应用一种新的方法来识别工作现场的危险 个人工人，以改进风险评估过程并帮助 指导预防职业健康问题的决策。

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.