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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 作为用于打击入侵病原体的化学武器群的一部分，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以产生过氧亚硝酸盐，该药物分解为能够损害蛋白质，脂质和DNA的物种。 关于DNA，鸟嘌呤对过氧亚硝酸盐特别敏感，并且已经鉴定出了许多氧化和硝化衍生物。 此外，在慢性炎症部位，过氧亚硝酸盐的生产过多。 实际上，已经建立了慢性炎症与癌症之间的炎症性肠综合征和结肠癌以及幽门螺杆菌感染和胃癌的联系。 在体外和细菌中的工作都表明，许多过氧亚硝酸盐诱导的DNA病变具有有效的诱变，并且具有不同程度的毒性。 但是，为了充分了解过氧亚硝酸盐过量生产的遗传后果，并揭示了其对癌症的贡献，我们将研究这些DNA病变在哺乳动物系统中的生物学加工。