Guanine sulphinate is a major stable product of photochemical oxidation of DNA 6-thioguanine by UVA irradiation

Ren, Xiaolin; Li, Feng; Jeffs, Graham; Zhang, Xiaohong; Xu, Yao-Zhong and Karran, Peter (2010). Guanine sulphinate is a major stable product of photochemical oxidation of DNA 6-thioguanine by UVA irradiation. Nucleic Acids Research, 38(6) pp. 1832–1840.

DOI: https://doi.org/10.1093/nar/gkp1165

Abstract

The DNA of patients taking the immunosuppressant and anticancer drugs azathioprine or 6-mercaptopurine contains 6-thioguanine (6-TG). The skin of these patients is selectively sensitive to ultraviolet A radiation (UVA) and they suffer an extremely high incidence of sunlight-induced skin cancer with long-term treatment. DNA 6-TG interacts with UVA to generate reactive oxygen species, which oxidize 6-TG to guanine sulphonate (G ^SO3). We suggested that G ^SO3 is formed via the reactive electrophilic intermediates, guanine sulphenate (G ^SO) and guanine sulphinate (G ^SO2). Here, GSO2 is identified as a significant and stable UVA photoproduct of free 6-TG, its 2'-deoxyribonucleoside, and DNA 6-TG. Mild chemical oxidation converts 6-TG into G^SO2, which can be further oxidized to G ^SO3—a stable product that resists further reaction. In contrast, G^SO2 is converted back to 6-TG under mild conditions. This suggests that cellular antioxidant defences might counteract the UVA-mediated photooxidation of DNA 6-TG at this intermediate step and ameliorate its biological effects. In agreement with this possibility, the antioxidant ascorbate protected DNA 6-TG against UVA oxidation and prevented the formation of G ^SO3.

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