Environmental exposure to organophosphates and onset of genotoxcity and oncogenes

摘要：环境毒素已被证明可引起遗传毒性和破坏基因组稳定的DNA损伤。 必须修复这一点，以防止肿瘤发生。最近，人们开始关注药物的相对安全性。 有机磷农药对环境的危害。在人的血液中发现有机磷残留物， 尿样、牲畜、禽类、土壤样本、饮用水和供人食用的食物。 长期接触农药，包括有机磷，会导致DMA损害的发生率增加 和染色体的变化，这表明杀虫剂可能是环境致癌物质。这位飞行员 因此，该项目将研究有机磷(IFP)引起的基因组不稳定性。慢性IFP 中毒与髓系化生和急性髓系白血病有关。这样的致癌特性 可能源于在人类淋巴细胞中观察到的IFP诱发的染色体异常。在此，我们建议 通过确定IFP诱导染色体的可能机制(S)来扩展这些观察 破坏并造成淋巴细胞的基因组不稳定。此外，我们还将鉴定可能的DNA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 海利格博士的毒理学专业知识和索博尔博士的DNA损伤和修复专业知识 与环境毒物相关的毒性和致癌机制，如 异苯硫磷

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