Environmental exposure to organophosphates and onset of genotoxcity and oncogenes

环境毒素已被证明可以引起基因毒性和破坏基因组稳定的DNA损伤，这些损伤必须 进行了修复以防止肿瘤发生。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。在人的血液和尿液中发现有机磷残留物 样本、牲畜、禽类、土壤样本、饮用水和供人类消费的食品。慢性 接触农药，包括有机磷，会导致DNA损伤的发生率增加， 染色体的变化，表明杀虫剂可能是环境致癌物质。这一试点项目 因此，我将研究有机磷(IFF)引起的基因组不稳定性。慢性IFF 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IFF在人类淋巴细胞中观察到的染色体异常。在此，我们建议 通过确定IFF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，我们还将确定可能的DNA修复系统 参与逆转IFP诱导的DNA损伤并确定DNA损伤反应通路 调节细胞对农药暴露的反应。相关性：这一试点项目将汇聚毒理学 海利格博士的专业知识和Sobol博士的DNA损伤和修复专业知识来剖析机制 与异苯硫磷等环境毒物有关的毒性和致癌性。

Environmental toxins have been shown to induce genotoxic and genome-destabilizing DNA 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 DNA 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 (IFF). Chronic IFF poisoning has been linked to myeloid metaplasia and acute myelogenous leukemia. Such oncogenic properties likely stem from IFF induced chromosomal aberrations observed in human lymphocytes. Here we propose to extend these observations by determining putative mechanism(s) utilized by IFF to induce chromosomal damage and create genomic instability in lymphocytes. In addition, we will identify DNA repair systems likely to be involved in reversing IFP-induced DNA damage and define the DNA damage response pathways that mediate the cellular reaction to pesticide exposure. 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.