MUTAGENESIS AND TOXICITY OF PEROXYNITRITE-INDUCED DNA LESIONS IN HUMAN CELLS

过氧亚硝酸盐引起的人类细胞 DNA 损伤的诱变和毒性

• 批准号: 7725168
• 负责人: Sarah Delaney
• 金额: $ 3.11万
• 依托单位: UNIVERSITY OF RHODE ISLAND
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7725168
• 关键词: Bacteria; Biological Process; Cells; Chemicals; Chronic; Colon Carcinoma; Computer Retrieval of Information on Scientific Projects Database; DNA; DNA lesion; Funding; Genetic; Grant; Guanine; Helicobacter Infections; Human; In Vitro; Inflammation; Inflammatory; Institution; Intestines; Invaded; Lesion; Leukocytes; Link; Lipids; Malignant Neoplasms; Mutagenesis; Nitrates; Nitric Oxide; Peroxonitrite; Proteins; Research; Research Personnel; Resources; Site; Source; Superoxides; Syndrome; System; Time; Toxic effect; United States National Institutes of Health; Work; macrophage; malignant stomach neoplasm; nitrate; pathogen

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. As part of the chemical armamentarium used to combat invading pathogens certain types of white blood cells produce reactive radicals. For instance, macrophages secrete superoxide and nitric oxide which combine to generate peroxynitrite, an agent that decomposes into species capable of damaging proteins, lipids, and DNA. With regard to DNA, guanine is particularly sensitive to peroxynitrite and numerous oxidized and nitrated derivatives have been identified. Furthermore, at sites of chronic inflammation peroxynitrite is overproduced for prolonged periods of time. Indeed, a link between chronic inflammation and cancer has been established for inflammatory bowel syndrome and colon cancer and also for Helicobacter pylori infection and gastric cancer. Work both in vitro and in bacteria has shown that many of the peroxynitrite-induced DNA lesions are potently mutagenic and have varying degrees of toxicity. However, in order to understand fully the genetic consequences of peroxynitrite overproduction, and to unravel its contributions to cancer, we will examine the biological processing of these DNA lesions within a mammalian system.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 作为用于对抗入侵病原体的化学武器的一部分，某些类型的白细胞会产生反应性自由基。 例如，巨噬细胞分泌超氧化物和一氧化氮，它们结合生成过氧亚硝酸盐，这种物质分解成能够破坏蛋白质、脂质和 DNA 的物质。 对于 DNA，鸟嘌呤对过氧亚硝酸盐特别敏感，并且已鉴定出许多氧化和硝化衍生物。 此外，在慢性炎症部位，过氧亚硝酸盐长时间过量产生。 事实上，炎症性肠综合征和结肠癌以及幽门螺杆菌感染和胃癌之间的慢性炎症和癌症之间存在联系。 体外和细菌中的研究表明，许多过氧亚硝酸盐诱导的 DNA 损伤具有强致突变性，并具有不同程度的毒性。 然而，为了充分了解过氧亚硝酸盐过量产生的遗传后果，并揭示其对癌症的影响，我们将研究哺乳动物系统内这些 DNA 损伤的生物处理过程。