Environment Oncology Partnership between Hampton University and UPCI (1of2)

汉普顿大学与 UPCI 之间的环境肿瘤学合作伙伴关系 (1of2)

• 批准号: 7503491
• 负责人: Simone Olivia Heyliger
• 金额: $ 14.22万
• 依托单位: HAMPTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-29 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7503491
• 关键词: Environment; Oncology; Partnership; between; Hampton

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.

描述（由申请人提供）：环境毒素已被证明会诱发基因毒性和基因组不稳定的 DMA 损伤，必须修复这些损伤以防止肿瘤发生。最近，人们开始担心有机磷农药对环境的相对安全性。人类血液和尿液样本、牲畜、鸟类、土壤样本、饮用水和人类食用的食品中都发现了有机磷残留。 长期接触包括有机磷酸酯在内的农药，会导致 DMA 损伤和染色体改变的发生率增加，这表明农药可能是环境致癌物。因此，该试点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。在这里，我们建议通过确定 IFP 用于诱导染色体损伤并在淋巴细胞中产生基因组不稳定的假定机制来扩展这些观察结果。此外，我们将鉴定可能参与逆转 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，以剖析异苯磷等环境毒物的毒性和致癌性相关机制。