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.

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