EXPOSURE, DOSE, BODY BURDEN AND HEALTH EFFECTS OF LEAD

铅是一种普遍存在的毒素，有几种生物措施可用 评估其吸收、沉积和对健康的影响。血样 铅(BLL)和锌原卟啉是常用的测量方法 对健康影响的预测不佳，并受到外部因素的影响 暴露、内部铅储存和个体之间的差异 铅的毒代动力学。铅吸收和负担的其他衡量标准 已经开发出(例如，DMSA可螯合铅、骨铅)，但是 这些都没有在对健康影响的前瞻性研究中进行评估。 此外，对个别因素如何可能 影响这些生物措施和健康效应之间的关系。 研究越来越多地指向发现相互作用 在个人因素和危险暴露之间。个体间 铅中毒动力学和毒性的差异可能是 部分是由遗传因素介导的，包括基因多态 差异结合铅并影响其新陈代谢的蛋白质。 越来越多的证据表明，β-氨基乙酰丙酸 脱水酶(ALAD)，一种多态的红细胞胞浆酶， 修饰铅~S的毒代动力学。我们建议进行一项前瞻性研究 BLLS、DMSA螯合铅、骨铅与健康的关系 影响(血红素合成、肾脏早期生物效应和功能、血液 压力、中枢神经系统和三叉神经节神经系统功能)。 ALAD基因型对这些关系的影响也将是 调查过了。这一群体非常适合调查 基因-环境相互作用，因为它的铅范围很广 暴露量，覆盖在美国观察到的整个范围，以及 新员工的数量。所有现有员工都将参加第一届 一年(N=640)，新招聘将招收2年(N=230)； 这两组人将与120名未接触过的对照组进行比较。 研究措施将在纵向上进行，在4个月内进行3次 一年的学习。这份提案提供了对该组合的理解 BLLS、骨铅和DMSA螯合铅的作用和影响 ALAD基因修饰在预测重要健康中的作用 结果。

Lead is a ubiquitous toxin and several biologic measures are available to assess its absorption, deposition, and health consequences. Blood lead (BLLs) and zinc protoporphyrin, commonly used measures, are poor predictors of health effects and are influenced by external exposure, internal lead stores, and interindividual differences in the toxicokinetics of lead. Other measures of lead absorption and burden have been developed (e.g., DMSA-chelatable lead, bone lead), but these have not been evaluated in prospective studies of health effects. Furthermore, there is little understanding of how individual factors may influence relations between these biologic measures and health effects. Increasingly, research has been directed at discovering interactions between individual factors and hazardous exposures. Interindividual differences in lead toxico-kinetics and toxicity are likely to be mediated, in part, by genetic factors, including polymorph-isms in proteins that differentially bind lead and affect its metabolism. Accumulating evidence suggests that delta-aminolevulinic acid dehydratase (ALAD), a polymorphic erythrocyte cytoplasmic enzyme, modifies lead~s toxicokinetics. We propose a prospective study of the relations among BLLs, DMSA-chelatable lead, bone lead, and health effects (heme synthesis, renal early biologic effects and function, blood pressure, and CNS and PNS function) in lead workers in South Korea. Effect modification of these relations by ALAD genotype will also be investigated. This population is uniquely suited to investigation of gene-environment interaction because of its broad range of lead exposures, covering the entire range observed in the U.S., and large numbers of new hires. All current workers will be enrolled in the first year (N=640) and new hires will be enrolled for 2 years (N=230); these two groups will be compared with 120 nonexposed controls. Study measures will be obtained longitudinally, 3 times during the 4 year study. This proposal offers an understanding of the composite roles of BLLs, bone lead, and DMSA-chelatable lead, and effect modification by ALAD genotype, in the prediction of important health outcomes.