DNA repair responses in human skin cells.
Sunlight and some environmental chemical agents produce lesions in the DNA of human skin cells that if unrepaired may interfere with normal functioning of these cells. The most serious outcome of such interactions may be malignancy. It is therefore important to develop an understanding of mechanisms by which the lesions may be repaired or tolerated without deleterious consequences. Our models for the molecular processing of damaged DNA have been derived largely from the study of bacterial systems. Some similarities but significant differences are revealed when human cell responses are tested against these models. It is also of importance to learn DNA repair responses of epidermal keratinocytes for comparison with the more extensive studies that have been carried out with dermal fibroblasts. Our experimental results thus far indicate similarities for the excision-repair of ultraviolet-induced pyrimidine dimers in human keratinocytes and fibroblasts. Both the monoadducts and the interstrand crosslinks produced in DNA by photoactivated 8-methoxypsoralen (PUVA) can be repaired in normal human fibroblasts but not in those from xeroderma pigmentosum patients. The monoadducts, like pyrimidine dimers, are probably the more mutagenic/carcinogenic lesions while the crosslinks are less easily repaired and probably result in more effective blocking of DNA function. It is suggested that a split-dose protocol that maximizes the production of crosslinks while minimizing the yield of monoadducts may be more effective and potentially less carcinogenic than the single ultraviolet exposure regimen in PUVA therapy for psoriasis.
D001419:Bacteria / Q000528:radiation effects; D004260:DNA Repair / Q000528:radiation effects*; D000078404:Epidermal Cells; D011564:Furocoumarins / Q000009:adverse effects; D006801:Humans; D011701:PUVA Therapy / Q000009:adverse effects; D010778:Photochemotherapy / Q000009:adverse effects; D011565:Psoriasis / Q000473:pathology; D011740:Pyrimidine Dimers / Q000502:physiology; D012867:Skin / Q000166:cytology* / Q000528:radiation effects; D014983:Xeroderma Pigmentosum / Q000473:pathology
D011564:Furocoumarins; D011740:Pyrimidine Dimers