Cyclosporin-A suppresses p53-dependent repair DNA synthesis and apoptosis following ultraviolet-B irradiation.
BACKGROUND
The combination of cyclosporin-A (CS-A) and ultraviolet-B (UV-B) irradiation is not recommended in the treatment of psoriasis, because risks of UV-B-induced skin cancer are increased. The recommendation, however, has not well been confirmed by basic researches.


OBJECTIVE
In this study, we investigated the effects of CS-A on UV-B-induced repair DNA synthesis, apoptosis and p53 expression.


METHODS
Following the short-term administration of CS-A (5 and 50 mg/kg/day) or vehicle (V) alone, female BALB/c mice, 8-10 weeks old, were treated with UV-B irradiation (100 and 500 mJ(2) cm) or tape stripping (TS). After the treatment, the effects of CS-A on the increased rate of epidermal DNA synthesis were examined by using 5'-bromodeoxyuridine (BrdU) pulse-labelling techniques. In separate experiments, the effects of CS-A on the number of sunburn cells, nick-end labelling+ cells and p53+ cells were examined 24 h after UV-B irradiation.


RESULTS
Cyclosporin-A significantly suppressed the UV-B-induced increase in BrdU uptake, which occurs to repair DNA damage, while there were no significant effects on the stripping (S)-induced increase or the rate of normal epidermal proliferation, which is not associated with any DNA injuries. The number of sunburn cells, nick-end labelling+ cells and p53+ cells was significantly reduced by pretreatment with CS-A.


CONCLUSIONS
Cyclosporin-A interferes with the self- protective mechanisms involved in both repair and apoptotic removal of UV-B-induced DNA damage. The loss of p53 expression is responsible for the effects of CS-A.
Sugie
N
N
Department of Dermatology, Shiga University of Medical Science, Otsu, Japan.
Fujii
N
N
Danno
K
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D001973:Bromodeoxyuridine; D002452:Cell Count; D016572:Cyclosporine / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects / Q000528:radiation effects; D004260:DNA Repair / Q000187:drug effects* / Q000528:radiation effects; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D005260:Female; D016158:Genes, p53 / Q000187:drug effects / Q000528:radiation effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D051379:Mice; D008807:Mice, Inbred BALB C; D013471:Sunburn / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*
D007166:Immunosuppressive Agents; D016159:Tumor Suppressor Protein p53; D016572:Cyclosporine; D004247:DNA; D001973:Bromodeoxyuridine