title: Topical nutlin-3a does not decrease photocarcinogenesis induced by simulated solar radiation in hairless mice.
abstract: BACKGROUND
  Nutlin-3a increases p53 levels after UVB radiation, which could result in a decrease in DNA damage and thus lead to a lower risk of non-melanoma skin cancer. Especially, organ transplant recipients might derive benefit from such a topical formulation with an active ingredient to prevent DNA damage.
  
  
  OBJECTIVE
  To investigate whether topical nutlin-3a can decrease photocarcinogenesis induced by simulated solar radiation.
  
  
  METHODS
  72 hairless C3.Cg/TifBomTac mice were treated 3 days/week topically with 100 μl nutlin-3a (9 mM) [Groups 1 and 3 (120 days)) or 100 μl vehicle (Group 2). Three hours later, all mice were exposed to simulated solar radiation (a radiometric equivalent of three standard erythema dose units).
  
  
  RESULTS
  The median time to tumours did not differ between the mice treated with nutlin-3a and with the vehicle. The median time to the first and second tumours did not differ between 'nutlin-3a-120 days' and vehicle-treated mice, but there was a small significant difference in the median time to the third tumour (211 vs. 196 days, P = 0.043). However, after Bonferroni correction, there was no difference at all.
  
  
  CONCLUSIONS
  Nutlin-3a had no reductive effect on photocarcinogenesis and we do not believe in nutlin-3a as a potential drug against DNA damage in a topical formulation for organ transplant patients.
authors.affiliation: Department of Dermatology, Copenhagen University Hospital, Copenhagen, Denmark. cler0001@bbh.regionh.dk
authors.forename: Catharina Margrethe
authors.initials: CM
authors.lastname: Lerche
authors.forename: Peter Alshede
authors.initials: PA
authors.lastname: Philipsen
authors.forename: Thomas
authors.initials: T
authors.lastname: Poulsen
authors.forename: Robert
authors.initials: R
authors.lastname: Gniadecki
authors.forename: Hans Christian
authors.initials: HC
authors.lastname: Wulf
mesh_terms: D000287:Administration, Topical; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D004249:DNA Damage; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D051379:Mice; D008812:Mice, Hairless; D010879:Piperazines / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000473:pathology / Q000517:prevention & control*; D013472:Sunlight / Q000009:adverse effects*; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D007093:Imidazoles; D010879:Piperazines; C482205:nutlin 3