Photocarcinogenesis of topical tazarotene and isotretinoin alone and in combination with valproic acid in hairless mice

Exp Dermatol. 2008 Nov;17(11):972-4. doi: 10.1111/j.1600-0625.2008.00733.x. Epub 2008 Jul 12.

Abstract

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.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Carcinogens / administration & dosage
  • Carcinogens / toxicity
  • Dermatologic Agents / administration & dosage
  • Dermatologic Agents / toxicity
  • Dose-Response Relationship, Radiation
  • Female
  • Isotretinoin / administration & dosage
  • Isotretinoin / toxicity*
  • Kaplan-Meier Estimate
  • Mice
  • Mice, Hairless
  • Nicotinic Acids / administration & dosage
  • Nicotinic Acids / toxicity*
  • Photochemical Processes
  • Skin / drug effects
  • Skin / pathology
  • Skin / radiation effects
  • Skin Neoplasms / chemically induced
  • Skin Neoplasms / pathology*
  • Ultraviolet Rays
  • Valproic Acid / administration & dosage
  • Valproic Acid / toxicity*

Substances

  • Carcinogens
  • Dermatologic Agents
  • Nicotinic Acids
  • Valproic Acid
  • tazarotene
  • Isotretinoin