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: 7474436
• 负责人: Ramune Reliene
• 金额: $ 7.7万
• 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 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7474436
• 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; 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; Numbers; OGG1 gene; Oral; Persons; Pilot Projects; Point Mutation; Pomegranate; Population; Prevention; Preventive; Primary Prevention; Rate; 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; 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）：