Environmental exposure to organophosphates and onset of genotoxcity and oncogenes

有机磷酸酯的环境暴露以及基因毒性和癌基因的发生

基本信息

批准号：
7692320
负责人：
Simone Olivia Heyliger
金额：
$ 6.09万
依托单位：
HAMPTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/7692320
关键词：
Acute Myelocytic Leukemia Aftercare Astrocytes Banana Birds Blast Cell Blood Carrots - dietary Cell Cycle Chemicals Chlorpyrifos Cholinesterase Inhibitors Chromosome Fragile Sites Chromosome abnormality Chronic Consumption DNA Damage DNA Repair Development Environment Environmental Carcinogens Environmental Exposure Environmental Health Exposure to Food Genetic Genome Genomic Instability Hand Health Human Incidence Individual Insecta Invasive Investigation Isoptera K-562 Lesion Link Livestock Lymphocyte Maize Myelogenous Myeloid Metaplasia Oligodendroglia Oncogenes Oncogenic Organophosphates Pathway interactions Pesticide Residues Pesticides Phenotype Pilot Projects Poisoning Population Property Relative (related person)Risk Safety Sampling Soil Techniques Toxic Environmental Substances Toxic effect Toxicology Urine Water Week Work Zea mays abstracting base carcinogenicity drinking water experience fruits and vegetables genotoxicity isofenphos leukemia leukemogenesis prevent repair enzyme repaired soil sampling stem toe corn toxic organophosphate insecticide exposure tumorigenesis

项目摘要

Abstract: Environmental toxins have been shown to induce genotoxic and genome-destabilizing DMA lesions that must be repaired to prevent oncogenesis. Recently, concerns have arisen regarding the relative safety of organophosphate pesticides to the environment. Organophosphate residues are found in human blood and urine samples, livestock, avian species, soil samples, drinking water and foods for human consumption. Chronic exposure to pesticides, including organophosphates, leads to an increased incidence of DMA damage and chromosomal alterations, suggesting that pesticides may act as environmental carcinogens. This pilot project will therefore study genomic instability induced by the organophosphate Isofenphos (IFP). Chronic IFP poisoning has been linked to myeloid metaplasia and acute myelogenous leukemia. Such oncogenic properties likely stem from IFP induced chromosomal aberrations observed in human lymphocytes. Here we propose to extend these observations by determining putative mechanism(s) utilized by IFP to induce chromosomal damage and create genomic instability in lymphocytes. In addition, we will identify DMA repair enzymes likely to be involved in reversing IFP-induced DNA damage. Relevance: This pilot project will converge the toxicology expertise of Dr. Heyliger and the DNA damage and repair expertise of Dr. Sobol to dissect mechanisms associated with toxicity and carcinogenicity associated with environmental toxicants such as isophenfos

摘要：已显示环境毒素可诱导基因组和基因组毒素DMA病变必须修复以防止肿瘤发生。最近，人们对有机磷酸盐农药到环境。在人血和尿液样品，牲畜，禽类，土壤样品，饮用水和食物供人类食用。长期暴露于包括有机磷酸盐在内的农药，导致DMA损伤的发生率增加和染色体的改变，表明农药可能是环境致癌物。这个飞行员因此，项目将研究由有机磷酸异苯酚（IFP）引起的基因组不稳定性。慢性IFP 中毒已与髓样化生和急性髓质白血病有关。这种致癌特性可能源自IFP诱导人淋巴细胞中观察到的染色体畸变。在这里我们建议通过确定IFP诱导染色体的假定机制来扩展这些观察结果损害并在淋巴细胞中产生基因组不稳定性。此外，我们将确定可能的DMA修复酶参与反向IFP诱导的DNA损伤。相关性：该试点项目将融合 Heyliger博士的毒理学专业知识以及SOBOL博士的DNA损害和维修专业知识以剖析与环境有毒物质相关的毒性和致癌性相关的机制，例如同芬费斯