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.
Purpose: 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.
Conclusion: 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.