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：环境毒素已被证明会诱发基因毒性和基因组不稳定 DMA 损伤必须对其进行修复以防止肿瘤发生。最近，人们对这种药物的相对安全性产生了担忧。有机磷农药对环境的影响。人体血液中发现有机磷残留尿液样本、牲畜、鸟类、土壤样本、饮用水和人类消费的食品。长期接触农药（包括有机磷酸酯）会导致 DMA 损害的发生率增加和染色体改变，表明农药可能是环境致癌物。这位飞行员因此，该项目将研究有机磷酸酯异芬磷（IFP）引起的基因组不稳定性。慢性IFP 中毒与骨髓化生和急性髓性白血病有关。这种致癌特性可能源于在人类淋巴细胞中观察到的 IFP 诱导的染色体畸变。在此我们建议通过确定 IFP 用于诱导染色体的假定机制来扩展这些观察结果损伤并造成淋巴细胞基因组不稳定。此外，我们将鉴定可能的 DMA 修复酶参与逆转 IFP 诱导的 DNA 损伤。相关性：该试点项目将汇聚 Heyliger 博士的毒理学专业知识和 Sobol 博士的 DNA 损伤和修复专业知识进行剖析与环境毒物相关的毒性和致癌性机制，例如异苯磷