Cyclobutane pyrimidine dimer formation and p53 production in human skin after repeated UV irradiation.
Substantial differences in DNA damage caused by a single UV irradiation were found in our previous study on skin with different levels of constitutive pigmentation. In this study, we assessed whether facultative pigmentation induced by repeated UV irradiation is photoprotective. Three sites on the backs of 21 healthy subjects with type II-III skin were irradiated at 100-600 J/m(2) every 2-7 days over a 4- to 5-week period. The three sites received different cumulative doses of UV (1900, 2900 or 4200 J/m(2)) and were biopsied 1 day after the last irradiation. Biomarkers examined included pigment content assessed by Fontana-Masson staining, melanocyte function by expression of melanocyte-specific markers, DNA damage as cyclobutane pyrimidine dimers (CPD), nuclear accumulation of p53, apoptosis determined by TUNEL assay, and levels of p21 and Ser46-phosphorylated p53. Increases in melanocyte function and density, and in levels of apoptosis were similar among the 3 study sites irradiated with different cumulative UV doses. Levels of CPD decreased while the number of p53-positive cells increased as the cumulative dose of UV increased. These results suggest that pigmentation induced in skin by repeated UV irradiation protects against subsequent UV-induced DNA damage but not as effectively as constitutive pigmentation.
Yamaguchi
Yuji
Y
Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Coelho
Sergio G
SG
Zmudzka
Barbara Z
BZ
Takahashi
Kaoruko
K
Beer
Janusz Z
JZ
Hearing
Vincent J
VJ
Miller
Sharon A
SA
D000328:Adult; D000951:Antigens, Neoplasm / Q000378:metabolism; D017209:Apoptosis / Q000528:radiation effects; D002452:Cell Count; D005260:Female; D006801:Humans; D058965:MART-1 Antigen; D008297:Male; D008543:Melanins / Q000378:metabolism; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D008562:Membrane Glycoproteins / Q000378:metabolism; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D010766:Phosphorylation / Q000528:radiation effects; D011740:Pyrimidine Dimers / Q000378:metabolism*; D012867:Skin / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014466:Ultraviolet Rays; D055815:Young Adult; D058951:gp100 Melanoma Antigen
D000951:Antigens, Neoplasm; D058965:MART-1 Antigen; C497234:MITF protein, human; C548667:MLANA protein, human; D008543:Melanins; D008562:Membrane Glycoproteins; D051739:Microphthalmia-Associated Transcription Factor; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D011740:Pyrimidine Dimers; D016159:Tumor Suppressor Protein p53; D058951:gp100 Melanoma Antigen; D014442:Monophenol Monooxygenase