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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 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）已经被用作有效的抗癌剂、免疫抑制剂和控制药物用于治疗炎性疾病50年。然而，与6-TG取代的DNA相关的致命威胁也引起了人们的注意。硫嘌呤类DNA碱基及其衍生物S-甲基巯基嘌呤（me 6-MP）和S-甲基硫鸟嘌呤（me 6-TG）作为内源性单线态氧敏化剂，可能成为DNA损伤源，这促使我们定量研究它们的光敏化能力。本研究采用了时间分辨激光和稳态光解等光化学技术。我们的研究结果表明，所有这些硫嘌呤具有产生单线态氧的量子产率约0.4的能力。然而，它们的光敏化能力显着下降，在光和氧气的存在下。第一次，在UVA照射的硫嘌呤单线态氧的生产直接观察到在1270 nm和定量表征。我们的研究结果为巯基嘌呤的分子事件提供了新的线索，这些分子事件可能是生物系统中危险活动的基础。