Environmental Oncology Partnership between Hampton University and UPCI (2 of 2)

描述(由申请人提供)：环境毒素已被证明可引起遗传毒性和破坏基因组稳定的DMA损伤，必须修复这些损伤以防止肿瘤发生。最近，人们开始关注有机磷农药对环境的相对安全性。有机磷残留存在于人的血液和尿液样本、牲畜、禽类、土壤样本、饮用水和人类消费的食物中。长期接触杀虫剂，包括有机磷，会导致DMA损伤和染色体改变的发生率增加，这表明杀虫剂可能是环境致癌物质。因此，这个试点项目将研究有机磷(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诱导的染色体异常。在这里，我们建议通过确定IFP用来诱导染色体损伤和在淋巴细胞中产生基因组不稳定性的可能机制(S)来扩大这些观察。此外，我们还将确定可能参与逆转IFP诱导的DMA损伤的DMA修复酶。相关性：该试点项目将汇集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，以剖析与异苯硫磷等环境毒物相关的毒性和致癌机制。

DESCRIPTION (provided by applicant): 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 DMA 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.