Epidermal p53 response and repair of thymine dimers in human skin after a single dose of ultraviolet radiation: effects of photoprotection.
A cellular p53 response, DNA repair enzymes and melanin pigmentation are important strategies utilized by skin keratinocytes against impairment caused by ultraviolet radiation (UVR). In this study a double-immunofluorescence technique was used to investigate UVR-induced thymine dimers and p53 protein simultaneously. Four healthy volunteers were irradiated on both sides of their buttock skin with a single dose of solar-simulating UVR. One side was pretreated with a topical sunscreen. Biopsies from different time-points were immunostained for visualization of thymine dimers, p53 and proliferation. One single physiological dose of UVR generated widespread formation of thymine dimers throughout the epidermis 4h after irradiation. The level of thymine dimers decreased over time and was followed by a p53 response in the same cells. A late proliferative response was also found. The formation of thymine dimers, the p53 response and the late proliferative response were partially blocked by topical sunscreen. Large inter-individual differences in the kinetics of thymine dimer formation and repair as well as in the p53 response were evident in both sunscreen-protected and unprotected skin.
Ling
G
G
Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala, Sweden. Gao.Ling@genpat.uu.se
Chadwick
C A
CA
Berne
B
B
Potten
C S
CS
Pontén
J
J
Pontén
F
F
D000328:Adult; D000368:Aged; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage; D011088:DNA Ligases / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique / Q000379:methods; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D008297:Male; D008543:Melanins / Q000378:metabolism / Q000528:radiation effects; D008875:Middle Aged; D011740:Pyrimidine Dimers / Q000378:metabolism*; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D013473:Sunscreening Agents / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014466:Ultraviolet Rays / Q000009:adverse effects*
D008543:Melanins; D011740:Pyrimidine Dimers; D013473:Sunscreening Agents; D016159:Tumor Suppressor Protein p53; D004247:DNA; D011088:DNA Ligases