Biomarkers of Organophosphate-Adducted Proteins

有机磷加合蛋白的生物标志物

• 批准号: 7630596
• 负责人: charles mark thompson
• 金额: $ 49.96万
• 依托单位: UNIVERSITY OF MONTANA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-15 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7630596
• 关键词: Accounting; Acetylcholinesterase; Acute; Address; Age; Aging; Agriculture; Antibodies; Biochemical; Biological; Biological Markers; Blood; Blood Tests; Carbamates; Cells; Chemicals; Child; Cholinergic Receptors; Cholinesterases; Chronic; Detection; Diagnostic Procedure; Diagnostic tests; Dose; Environmental Health; Erythrocytes; Esters; Event; Exposure to; Food Contamination; Goals; Grant; Health; Human; Insecticides; Isotopically-Coded Affinity Tagging; Lead; Liquid substance; Mass Spectrum Analysis; Measures; Methods; Molecular; Monitor; Neuroblastoma; Neurologic; Organ; Organophosphates; Outcome; Pathway interactions; Pattern; Peptides; Pesticides; Phosphorylation; Poison Control Centers; Poisoning; Proteins; Proteome; Public Health; Radiolabeled; Regulation; Reporter; Reporting; Research; Research Personnel; Risk; Risk Assessment; Role; Safety; Saliva; Science Policy; Serum; Site; Structure; Testing; Therapeutic; Therapeutic Intervention; Time; Tissues; Toxic effect; Trust; adduct; base; combat; nerve gas; neurotoxicity; programs; radiotracer; toxic organophosphate insecticide exposure; trait; true biomarker

The short-term goals of this application are to identify adducted and altered protein biomarkers that correlate with organophosphate (OP) insecticide exposure and to use these biomarkers to generate antibodies to validate the detection of these biomarkers in biological fluids. Over 100 million pounds of OP insecticides are used each year but lead to over 25,000 reports to poison control centers each year including 10,000 involving children under age six. These reports only account for acute poisoning events and do not include low dose or chronic exposures. In addition to general exposure and food contamination, the safety of OPs is a large public health concern because OPs share chemical traits, structure and biological mechanism with nerve gas agents. These concerns are elevated by an array of neurologic and non-neurologic sequelae that have been reported in connection with exposure to OPs. To combat, monitor and provide therapeutic intervention, a blood cholinesterase test (BCT) has been conducted for decades. However, the test is limited and inadequate to assess OP exposure and its shortcomings identified by an EPA report questioned the merit of the BCT and suggested the need to examine true biomarkers of exposure. At this time, there is a serious void in effective tests of OP exposure. New tests are needed that are sensitive, selective, operate in real time and are based on reliable, well-characterized OP-biomarkers derived from exacting molecular events that correlate with cellular, tissue, organ or systemic toxicity. The long range goal of our research is to identify OP-adducted and/or OP-altered protein biomarkers that are associated with OP-induced sequelae and to develop diagnostic methods and tests that assess the human health risk and aid therapeutic action. For the proposed grant period, we will address the following specific aims: SA 1. Show that OP's result in highly specific OP-AChE adducts that can be identified and differentiated by antibodies. SA2. Identify and characterize OP-adducted protein biomarkers in SH-SY5Y neuroblastoma cells using OP-reporter molecules. SA3. Identify and characterize OP-protein biomarkers from human saliva, human serum and human erythrocytes and SA4. Prepare customized antibodies that recognize OP-adducted proteins identified in SA-II and SA-III and develop efficient diagnostic tests to identify and quantify OP-protein adducts.

该应用的短期目标是识别与关联的加合物和改变的蛋白质生物标志物 与有机磷酸盐（OP）杀虫剂暴露，并使用这些生物标志物生成抗体 验证在生物流体中检测这些生物标志物。超过1亿磅的OP杀虫剂 每年使用，但每年都会有25,000多个报告，包括10,000 涉及六岁以下的儿童。这些报告仅考虑急性中毒事件，不包括 低剂量或慢性暴露。除了普遍的暴露和食物污染外，OP的安全性是 大型公共卫生问题是因为OPS与 神经气体剂。这些关注者通过一系列神经系统和非神经学后遗症提升了这些问题 已经报告了与OPS接触有关的。战斗，监测和提供治疗 干预，几十年来已经进行了血液胆碱酯酶测试（BCT）。但是，测试是有限的 EPA报告不足以评估OP暴露及其缺点提出了质疑 BCT的优点，并建议需要检查真正的暴露生物标志物。目前有一个 在有效的OP暴露测试中，严重的空隙。需要敏感，选择性的新测试 实时，基于可靠的，良好的op-biomarkers，该标志物从严格的分子中得出 与细胞，组织，器官或全身毒性相关的事件。 我们研究的远距离目标是识别开发和/或开发的蛋白质生物标志物 与操作引起的后遗症相关，并开发评估人类的诊断方法和测试 健康风险和援助治疗行动。在拟议的赠款期间，我们将讨论以下特定 目的：sa 1。显示OP的结果中可以识别的高度特定的操作 - 痛苦加合物 通过抗体区分。 SA2。识别和表征SH-SY5Y中的操作蛋白生物标志物 神经母细胞瘤细胞使用op-Reporter分子。 SA3。识别和表征OP蛋白生物标志物 来自人类唾液，人血清和人类红细胞和SA4。准备定制的抗体 识别在SA-II和SA-III中鉴定出的操作蛋白质，并开发有效的诊断测试以识别 并量化OP蛋白加合物。