LIGHT-INDUCED DNA BASE EXCITATION, DEACTIVATION AND OXIDATION

光诱导 DNA 碱基激发、失活和氧化

• 批准号: 8166141
• 负责人: Ruomei Gao
• 金额: $ 9.74万
• 依托单位: JACKSON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8166141
• 关键词: 6-Mercaptopurine; Antineoplastic Agents; Attention; Azathioprine; Computer Retrieval of Information on Scientific Projects Database; DNA; DNA Damage; Disease; Drug Controls; Event; Funding; Grant; Immunosuppressive Agents; Inflammatory; Institution; Lasers; Light; Molecular; Oxygen; Photosensitization; Production; Research; Research Personnel; Resources; Singlet Oxygen; Source; Techniques; Thioguanine; Time; United States National Institutes of Health; analog; base; biological systems; irradiation; oxidation; photolysis; quantum; thiopurine

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. Thiopurine DNA base analogues, azathioprine (Aza), 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) have been used as effective anti-cancer agents, immunosuppressants and control drugs in the treatment of inflammatory disorders for five decades. Nevertheless, fatal threat associated with 6-TG-substituted DNA was also caught attention. The possibility that thiopurines DNA bases and their derivatives of S-methylmercaptopurine (me6-MP) and S-methylthioguanine (me6-TG) thiopurines may act as an endogenous singlet oxygen sensitizer and provide a source of DNA damage promoted us to quantitatively study their photosensitization ability. Photochemical techniques such as time-resolved laser and steady-state photolysis are employed in this study. Our results show that all of these thiopurines possess the ability to produce singlet oxygen with quantum yields ~ 0.4. However, their photosensitization ability was decreased dramatically under light in the presence of oxygen. For the first time, upon UVA irradiation of thiopurines singlet oxygen production was observed directly at 1270 nm and characterized quantitatively. Our results shine new light on the molecular events of thiopurines that may underlie risky activity in biological systems.

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。 硫嘌呤 DNA 碱基类似物、硫唑嘌呤 (Aza)、6-巯基嘌呤 (6-MP) 和 6-硫鸟嘌呤 (6-TG) 五十年来一直被用作治疗炎症性疾病的有效抗癌剂、免疫抑制剂和控制药物。然而，与 6-TG 取代 DNA 相关的致命威胁也引起了人们的关注。硫嘌呤DNA碱基及其衍生物S-甲硫基嘌呤(me6-MP)和S-甲硫鸟嘌呤(me6-TG)硫嘌呤可能作为内源性单线态氧敏化剂并提供DNA损伤源，这促使我们定量研究它们的光敏性能力。本研究采用了时间分辨激光和稳态光解等光化学技术。我们的结果表明，所有这些硫代嘌呤都具有产生单线态氧的能力，量子产率约为 0.4。然而，在有氧存在的情况下，它们的光敏能力急剧下降。首次在 UVA 照射下直接在 1270 nm 处观察到硫嘌呤单线态氧的产生并进行定量表征。我们的结果为硫嘌呤的分子事件提供了新的线索，硫嘌呤可能是生物系统中危险活动的基础。