Photosensitization of guanine-specific DNA damage by a cyano-substituted quinoxaline di-N-oxide.
The cyano-substituted quinoxaline di-N-oxide (2) is a potential antitumor agent, which selectively kills hypoxic cells. While investigating this drug's potential ability to act as a surrogate for O(2) in DNA damage processes, we discovered that 2 produces alkali-labile lesions selectively at 2'-deoxyguanosine positions upon irradiation in the UV-A (lambda(max) = 350 nm) region. Strand damage is induced in single-stranded and double-stranded substrates, with the latter being slightly more susceptible to lesion formation. Alkaline-labile lesions are formed under aerobic and anaerobic conditions. The efficient formation of alkali-labile lesions by 2 suggests that this molecule may exhibit phototoxicity. Subsequent investigation of this process suggests that photoexcited 2 damages DNA via a type I process. The results of experiments aimed at determining the involvement of singlet O(2) are ambiguous and indicate that commonly used experimental tests for this species may be less definitive than often thought. The involvement of other reactive oxygen species in strand damage, such as hydroxyl radical, is ruled out.[1]References
- Photosensitization of guanine-specific DNA damage by a cyano-substituted quinoxaline di-N-oxide. Fuchs, T., Gates, K.S., Hwang, J.T., Greenberg, M.M. Chem. Res. Toxicol. (1999) [Pubmed]
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