LIGHT-INDUCED DNA BASE EXCITATION, DEACTIVATION AND OXIDATION

Jackson State University, Jackson MS

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Abstract

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.