Induction and excretion of ultraviolet-induced 8-oxo-2'-deoxyguanosine and thymine dimers in vivo: implications for PUVA.
Molecular epidemiology has linked ultraviolet-induced DNA damage with mutagenesis and skin carcinogenesis. Ultraviolet radiation may damage DNA in one of two ways: either directly, leading to lesions such as cyclobutane thymine dimers (T<>T), or indirectly, via photosensitizers that generate free radical species that may ultimately produce such oxidative lesions as 8-oxo-2'-deoxyguanosine. We report the results of a pilot, case control study in which seven, healthy, human volunteers (skin type II; aged 23-56 y; three male, four female) received a suberythemal dose of whole body irradiation from ultraviolet-A-emitting fluorescent tubes used in psoralen plus ultraviolet A therapy. First void, mid-stream urine samples were collected pre-exposure and daily postexposure, for up to 13 d. Analysis of urinary 8-oxo-2'-deoxyguanosine and cyclobutane thymine dimers was by competitive enzyme-linked immunosorbent assay (interassay coefficient of variation < or = 10%) and compared with a matched, control group of unirradiated individuals. A maximal increase in levels of urinary 8-oxo-2'-deoxyguanosine was seen 4 d post-ultraviolet exposure. A subsequent reduction was noted, before finally returning to baseline. Similarly, cyclobutane thymine dimer levels peaked 3 d postexposure, before returning to baseline. In contrast to the 8-oxo-2'-deoxyguanosine analysis, however, a second peak was noted at days 9-11, before again returning to baseline. This is the first report examining urinary 8-oxo-2'-deoxyguanosine and cyclobutane thymine dimers following ultraviolet exposure of healthy human subjects. This work illustrates the induction and time course for excretion of ultraviolet-induced lesions, perhaps alluding to repair and ultimately offering the potential to define psoralen plus ultraviolet A dosage regimes in terms of minimizing DNA damage and hence cancer risk.
Cooke
M S
MS
Oxidative Stress Group, Division of Chemical Pathology, University of Leicester, RKCSB, Leicester Royal Infirmary NHS Trust, PO Box 65, Leicester LE2 7LX, UK. msc5@le.ac.uk
Evans
M D
MD
Burd
R M
RM
Patel
K
K
Barnard
A
A
Lunec
J
J
Hutchinson
P E
PE
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D016022:Case-Control Studies; D004249:DNA Damage / Q000528:radiation effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000652:urine; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011701:PUVA Therapy; D010865:Pilot Projects; D011565:Psoriasis / Q000209:etiology; D011740:Pyrimidine Dimers / Q000378:metabolism*; D015203:Reproducibility of Results; D012878:Skin Neoplasms / Q000209:etiology; D014466:Ultraviolet Rays
D011740:Pyrimidine Dimers; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine