Topical calcineurin inhibitors decrease the production of UVB-induced thymine dimers from hairless mouse epidermis.
BACKGROUND
An increased incidence of ultraviolet-light-related skin tumours is a well-known problem in patients undergoing posttransplantation immunosuppression with systemic calcineurin inhibitors such as cyclosporine A or tacrolimus. UV-related carcinogenesis as a consequence of long-term treatment of sun-exposed sites with topical calcineurin inhibitors is therefore of theoretical concern.


RESULTS
In this study, we show that tacrolimus acts as a UVB filter when incorporated into liposome membranes. In hairless mice pretreated with 1% pimecrolimus cream, 0.1% tacrolimus ointment or vehicle, the amount of epidermal thymine dimers, measured 1 h after 1 J/cm2 of UVB irradiation, was decreased by 89, 84 and 47%, respectively, as compared to untreated mice. Forty-eight hours after UVB irradiation, 97, 89 and 93% of epidermal thymine dimer levels were removed in pimecrolimus-, tacrolimus- or vehicle-treated mice, respectively. In contrast, 69% of thymine dimers, originally present in much higher amounts than in treated mice, were removed from untreated controls. UVB-induced apoptosis was less pronounced in treated mice.


CONCLUSIONS
Taken together, these results suggest that topical calcineurin inhibitors prevent DNA photodamage due to a filter effect of both vehicle and active components, whereas they do not affect the clearance of DNA photoproducts.
Tran
Christian
C
Department of Dermatology, University Hospital, Geneva, Switzerland. christian.tran@hcuge.ch
Lübbe
Jann
J
Sorg
Olivier
O
Doelker
Laurence
L
Carraux
Pierre
P
Antille
Christophe
C
Grand
Denise
D
Leemans
Evelyne
E
Kaya
Gürkan
G
Saurat
Jean-Hilaire
JH
D000279:Administration, Cutaneous; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D065095:Calcineurin Inhibitors; D004249:DNA Damage / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008081:Liposomes; D051379:Mice; D008812:Mice, Hairless; D019696:Peptidylprolyl Isomerase / Q000037:antagonists & inhibitors; D014677:Pharmaceutical Vehicles; D011740:Pyrimidine Dimers / Q000037:antagonists & inhibitors* / Q000528:radiation effects; D012867:Skin / Q000187:drug effects* / Q000528:radiation effects; D013473:Sunscreening Agents / Q000494:pharmacology; D016559:Tacrolimus / Q000031:analogs & derivatives / Q000494:pharmacology; D014466:Ultraviolet Rays / Q000009:adverse effects*
D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors; D008081:Liposomes; D014677:Pharmaceutical Vehicles; D011740:Pyrimidine Dimers; D013473:Sunscreening Agents; C117268:pimecrolimus; D019696:Peptidylprolyl Isomerase; D016559:Tacrolimus