The in situ repair kinetics of epidermal thymine dimers and 6-4 photoproducts in human skin types I and II.
We assessed the in situ time-dependent loss of epidermal thymine dimers and 6-4 photoproducts in skin types I and II after exposure to two minimal erythema doses of solar-simulating radiation on previously unexposed buttock skin. Using quantitative image analysis, we evaluated biopsy sections stained with monoclonal antibodies. We then made comparisons, in the same volunteers, with unscheduled DNA synthesis, which is a direct marker of overall excision repair. Removal of thymine dimers was slow (half-life = 33.3 h), with high levels of lesions still present 24 h post-irradiation; some lesions were still present at 7 d. In contrast, removal of 6-4 photoproducts was rapid (half-life = 2.3 h), the decay kinetics of which correlated better with the decline in epidermal unscheduled DNA synthesis (half-life = 7.1 h). These data show that as in mouse, monkey, and in vitro models, the 6-4 photolesion is repaired preferentially in human epidermis in situ. They also raise the possibility that poor thymine dimer repair may be a feature of skin types I and II, who are more prone to skin cancer than are types III and IV. There was an inverse relationship between the onset of erythema and 6-4 photoproduct repair, suggesting that this repair process initiates erythema.
Young
A R
AR
Department of Photobiology, St. John's Institute of Dermatology, St.Thomas' Hospital, London, United Kingdom.
Chadwick
C A
CA
Harrison
G I
GI
Hawk
J L
JL
Nikaido
O
O
Potten
C S
CS
D000328:Adult; D002081:Buttocks; D004247:DNA / Q000096:biosynthesis; D004260:DNA Repair; D004817:Epidermis / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D012867:Skin / Q000528:radiation effects*; D012879:Skin Physiological Phenomena; D013472:Sunlight; D013941:Thymine / Q000737:chemistry / Q000502:physiology*; D013997:Time Factors
D004247:DNA; D013941:Thymine