Photocarcinogenesis of topical tazarotene and isotretinoin alone and in combination with valproic acid in hairless mice.
Retinoids and the histone deacetylase inhibitor valproic acid have shown anticancer properties, but the photocarcinogenic or photoprotective effect is unclear. Therefore, we investigated whether a topical formulation of valproic acid is photocarcinogenic or photoprotective in hairless female C3.Cg/TifBomTac immunocompetent mice exposed to simulated solar radiation (SSR) and whether valproic acid changes the effect of the retinoids: tazarotene and isotretinoin. The products were applied on the dorsal skin of 400 mice (five times weekly) followed by SSR (three times weekly) 3-4 h after the application. This was performed during 12 months or until death. Tumors appeared sooner in groups treated with tazarotene and isotretinoin compared with that of the group treated with valproic acid and the control group. The present study shows that valproic acid alone is not photocarcinogenic or photoprotective in hairless mice. When valproic acid is combined with tazarotene or isotretinoin, it does not change their photocarcinogenicity significantly.
Lerche
Catharina M
CM
Philipsen
Peter A
PA
Sehested
Maxwell
M
Wulf
Hans Christian
HC
D000279:Administration, Cutaneous; D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000633:toxicity; D004307:Dose-Response Relationship, Radiation; D005260:Female; D015474:Isotretinoin / Q000008:administration & dosage / Q000633:toxicity*; D053208:Kaplan-Meier Estimate; D051379:Mice; D008812:Mice, Hairless; D009539:Nicotinic Acids / Q000008:administration & dosage / Q000633:toxicity*; D055668:Photochemical Processes; D012867:Skin / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D012878:Skin Neoplasms / Q000139:chemically induced / Q000473:pathology*; D014466:Ultraviolet Rays; D014635:Valproic Acid / Q000008:administration & dosage / Q000633:toxicity*; D012176:Retinoids
D002273:Carcinogens; D003879:Dermatologic Agents; D015474:Isotretinoin; D009539:Nicotinic Acids; D014635:Valproic Acid; C086827:tazarotene; D012176:Retinoids