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: 7410219
• 负责人: Simone Olivia Heyliger
• 金额: $ 14.57万
• 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/7410219
• 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）：已证明环境毒素可诱导必须修复的基因组和基因组毒素DMA病变，以防止造成肿瘤。最近，人们对有机磷酸盐农药对环境的相对安全产生了担忧。在人类血液和尿液样本，牲畜，禽类，土壤样品，饮用水和食物中发现有机磷酸盐残留物。 长期暴露于包括有机磷酸盐在内的农药导致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，该初步项目将研究有机磷酸异氟（IFP）引起的基因组不稳定性。慢性IFP中毒已与髓样变质和急性髓质白血病有关。这种致癌特性可能源于IFP诱导人淋巴细胞中观察到的染色体畸变。在这里，我们建议通过确定IFP使用的推定机制来诱导染色体损伤并在淋巴细胞中产生基因组不稳定性来扩展这些观察结果。此外，我们将确定可能参与IFP诱导DMA损伤的DMA修复酶。相关性：该试点项目将融合Heyliger博士的毒理学专业知识，以及Sobol博士的DNA损害和修复专业知识，以剖析与毒性和致癌性与环境毒物相关的机制，例如同源物。