Guanine sulphinate is a major stable product of photochemical oxidation of DNA 6-thioguanine by UVA irradiation.
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, G(SO2) 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).
Ren
Xiaolin
X
Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Herts. EN6 3LD, UK.
Li
Feng
F
Jeffs
Graham
G
Zhang
Xiaohong
X
Xu
Yao-Zhong
YZ
Karran
Peter
P
D001190:Arylsulfonates / Q000737:chemistry*; D001205:Ascorbic Acid / Q000737:chemistry; D004247:DNA / Q000737:chemistry; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry; D010084:Oxidation-Reduction; D055668:Photochemical Processes; D013440:Sulfides / Q000737:chemistry; D013866:Thioguanine / Q000737:chemistry / Q000528:radiation effects*; D014466:Ultraviolet Rays
D001190:Arylsulfonates; D013440:Sulfides; C520547:guanine-6-sulfonate; D006147:Guanine; D004247:DNA; D013866:Thioguanine; D001205:Ascorbic Acid; C033479:sodium sulfide