Prevention of Genetic Instability by Pomegranate in Ogg1/Myh Deficient Mice

石榴预防 Ogg1/Myh 缺陷小鼠的遗传不稳定性

• 批准号: 7588074
• 负责人: Ramune Reliene
• 金额: $ 0.13万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7588074
• 关键词: Antioxidants; Chemopreventive Agent; Clinical; Colorectal; DNA; DNA Repair; DNA Sequence Rearrangement; DNA strand break; Data; Drug or chemical Tissue Distribution; Ellagic Acid; Epidemiology; Food Interactions; Frequencies; Fruit; Genes; Genetic; Genetic Polymorphism; Genetic Risk; Genome; Goals; Intake; Kidney; Lesion; Link; Lung; Malignant Neoplasms; Malignant neoplasm of urinary bladder; Mission; Mus; OGG1 gene; Oral; Persons; Pilot Projects; Point Mutation; Pomegranate; Population; Prevention; Preventive; Primary Prevention; Recurrent Malignant Neoplasm; Research; Risk; Role; Susceptibility Gene; Testing; United States National Institutes of Health; Wild Type Mouse; base; cancer prevention; cancer risk; dietary antioxidant; drinking water; fruits and vegetables; mutation carrier; oxidative DNA damage; oxidative damage; pre-clinical; prevent; repaired; tumor

DESCRIPTION (provided by applicant): Large numbers of cancers are linked to inheritance of susceptibility genes, especially for DNA repair. For example, alterations in OGG1 and MYH genes are associated with elevated risk of colorectal, lung, kidney and bladder cancer. Likewise, Ogg1/Myh deficient mice are prone to tumors. OGG1 and MYH genes are involved in the repair of oxidative DNA damage. Oxidative DNA damage can result in deleterious rearrangements in our genome leading to cancer. Therefore, antioxidants may reduce the level of oxidative DNA damage and rearrangements, hence prevent cancer. Pomegranate contains very high levels of antioxidants compared to other fruits and vegetables and may help reduce cancer risk. The goal of this pre-clinical pilot study is to understand whether pomegranate intake can reduce the level of genome rearrangements. Ogg1/Myh deficient mice will be treated with pomegranate extract (PomX) in their drinking water and genome rearrangements, including point mutations and deletions, will be determined in PomX treated mice and control mice receiving normal drinking water. If PomX reduces genome rearrangements, it will suggest that PomX may act as a cancer preventive agent. This pilot study would provide a justification to examine the long-term chemopreventive effect of PomX. These studies are significant to the mission of the National Institute of Health, because they will (i) advance our understanding of gene-nutrient interactions in the modulation of cancer risk, (ii) investigate the mechanisms of action of dietary antioxidants, and (iii) test a new strategy to prevent cancer in persons at increased genetic risk. This research could be transferred to the clinical setting for prevention of primary and recurrent cancers, especially in OGG1 and MYH mutation carriers. In addition, intake of pomegranate products could be recommended to help reduce cancer throughout the population.

描述（由申请人提供）： 大量癌症与易感基因的遗传有关，尤其是 DNA 修复基因。例如，OGG1 和 MYH 基因的改变与结直肠癌、肺癌、肾癌和膀胱癌的风险升高相关。同样，Ogg1/Myh 缺陷的小鼠也容易患肿瘤。 OGG1 和 MYH 基因参与 DNA 氧化损伤的修复。 DNA 氧化损伤会导致基因组发生有害的重排，从而导致癌症。因此，抗氧化剂可以降低氧化DNA损伤和重排的水平，从而预防癌症。与其他水果和蔬菜相比，石榴含有非常高水平的抗氧化剂，可能有助于降低癌症风险。这项临床前试点研究的目的是了解摄入石榴是否可以降低基因组重排的水平。 Ogg1/Myh 缺陷小鼠将在饮用水中加入石榴提取物 (PomX) 进行处理，并在 PomX 处理的小鼠和接受正常饮用水的对照小鼠中确定基因组重排，包括点突变和缺失。如果 PomX 减少基因组重排，则表明 PomX 可能充当癌症预防剂。这项初步研究将为检验 PomX 的长期化学预防作用提供依据。这些研究对美国国立卫生研究院的使命具有重要意义，因为它们将（i）增进我们对调节癌症风险中基因-营养相互作用的理解，（ii）研究膳食抗氧化剂的作用机制，以及（iii）测试一种新策略，以预防遗传风险较高人群的癌症。这项研究可以转移到临床环境中，用于预防原发性和复发性癌症，特别是 OGG1 和 MYH 突变携带者。此外，建议摄入石榴产品以帮助减少整个人群的癌症。