PORPHYRIN PROFILES AS BIOMARKERS OF TRACE METAL EXPOSURE AND TOXICITY

拟议研究的目的是验证 尿卟啉谱测量作为汞（Hg）的生物标志物 汞暴露、汞引起的神经行为效应和人体汞负荷 科目 长期目标是提供一个敏感和准确的 汞暴露的生物标志物和可用于减少汞暴露的影响 低汞人群汞中毒发生率和严重程度 环境暴露。 该项目的具体目标是：（1）描述人类个体 尿卟啉和尿汞排泄率的变异性 样本，并确定在何种程度上当场尿液样本， 代表24小时卟啉和汞排泄率，（2）测定 尿卟啉作为亚慢性和 慢性低浓度汞暴露;（3）测定尿汞敏感性 卟啉作为与低水平相关的神经效应的量度 汞暴露;（4）测定尿卟啉作为汞暴露的敏感性。 测量汞的体内负荷。 这些目标将通过以下方式实现： 评价尿卟啉谱与它们的相关性 具体测量汞暴露、神经行为功能和 受试者（牙医和牙科助理）的累积汞剂量 特征明确的、长期的、低水平的汞暴露， 居住在超级基金危险废物场地附近的人所经历的。 使用已建立的动物完成的其他特定目的 模型，是（5）定义尿卟啉浓度作为定量 测量肾脏中的可移动汞;（6）确定化学物质 非典型卟啉结构和生化病因学， “前原卟啉”，由接触汞的动物和人类排泄。 这些研究的预期结果是一个良好表征的生物标志物 基于目标组织对汞的生物反应， 大大加强对低水平汞接触和潜在汞排放的评估， 对人体的毒性。 这些研究还将进一步确定 生物化学机制，其基础的特异性 汞暴露的卟啉反应。

The objective of the proposed research is to validate the efficacy of urinary porphyrin profile measurements as a biomarker of mercury (Hg) exposure, Hg-induced neurobehavioral effects and Hg body burden in human subjects. The long-term goal is to provide a sensitive and accurate biomarker of Hg exposure and effects which can be used to reduce the incidence and severity of Hg toxicity in people with low-level environmental exposure. The specific aims of the project are to (1) describe individual human variability in urinary porphyrin and Hg excretion rates in spot urine samples, and determine the extent to which spot urine samples are representative of 24 hour porphyrin and Hg excretion rates, (2) determine the sensitivity of urinary porphyrins as a measure of sub-chronic and chronic low-level Hg exposure, (3) determine the sensitivity of urinary porphyrins as a measure of neurological effects associated with low-level Hg exposure, and (4) determine the sensitivity of urinary porphyrins as a measure of Hg body burden. These objectives will be accomplished by evaluating urinary porphyrin profiles with respect to their correlation with specific measures of Hg exposure, neurobehavioral function and cumulative Hg dose among subjects (dentists and dental assistants) with well-characterized, prolonged, low-level Hg exposure comparable to that experienced by persons residing near Superfund hazardous waste sites. Additional specific aims, to be accomplished using an established animal model, are to (5) define urinary porphyrin concentrations as a quantitative measure of mobilizable Hg in the kidney and (6) define the chemical structure and biochemical etiology of an atypical porphyrin, "precoproporphyrin", excreted by mercury-exposed animals and humans. The anticipated outcome of these studies is a well characterized biomarker based on a biological response to Hg in target tissues, which will significantly enhance the assessment of low-level Hg exposure and potential toxicity in human subjects. These studies will also further define the biochemical mechanisms which underlie the specificity of the porphyrinogenic response to Hg exposure.