Biomarkers of Organophosphate-Adducted Proteins

有机磷加合蛋白的生物标志物

• 批准号: 7485203
• 负责人: charles mark thompson
• 金额: $ 50.71万
• 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/7485203
• 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; Numbers; Organ; Organophosphates; Outcome; Pathway interactions; Pattern; Peptides; Pesticides; Phosphorylation; Poison Control Centers; Poisoning; Proteins; Proteome; Public Health; Radiolabeled; Range; Rate; 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; United States Environmental Protection Agency; Urination; adduct; base; nerve gas; neurotoxicity; programs; radiotracer; toxic organophosphate insecticide exposure; trait

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.

本申请的短期目标是鉴定与细胞凋亡相关的内收和改变的蛋白质生物标志物。 与有机磷（OP）杀虫剂接触，并使用这些生物标志物产生抗体， 验证这些生物标志物在生物流体中的检测。超过1亿磅的OP杀虫剂 每年都有超过25，000份中毒控制中心报告，其中包括10，000份 涉及六岁以下儿童这些报告仅说明急性中毒事件，不包括 低剂量或慢性暴露。除了一般接触和食品污染外，OP的安全性 这是一个很大的公共卫生问题，因为OP与 神经毒气一系列神经和非神经后遗症加剧了这些担忧， 与暴露于OP有关。打击、监测和提供治疗 为了预防和干预，血液胆碱酯酶测试（BCT）已经进行了几十年。然而，测试是有限的 不足以评估OP暴露及其缺陷，EPA报告质疑 他指出，BCT的优点，并建议需要检查真正的生物标志物的接触。在这个时候，有一个 OP暴露的有效测试中严重无效。需要新的检测方法，这些方法敏感，有选择性， 真实的时间，并基于可靠的，充分表征的OP-生物标志物，来自精确的分子生物学。 与细胞、组织、器官或全身毒性相关的事件。 我们研究的长期目标是鉴定OP-加合和/或OP-改变的蛋白质生物标志物， 与OP引起的后遗症相关，并开发评估人类的诊断方法和测试 健康风险和辅助治疗作用。在建议的资助期内，我们会处理以下具体事宜 目标：SA 1.表明OP的结果是高度特异性的OP-AChE加合物，可以识别， 由抗体区分。SA 2.在SH-SY 5 Y中鉴定和表征OP加合蛋白生物标志物 神经母细胞瘤细胞使用OP-报告分子。SA 3.识别和表征OP蛋白生物标志物 从人唾液、人血清和人红细胞和SA 4中。制备定制的抗体， 识别SA-II和SA-III中鉴定的OP加合蛋白，并开发有效的诊断测试， 并定量OP-蛋白加合物