Early inflammatory changes in the skin of SENCAR and C57BL/6 mice following exposure to 12-O-tetradecanoylphorbol-13-acetate.

Tumor-promoting phorbol esters are potent inflammatory agents. Inflammation has long been associated with carcinogenesis, particularly the promotion phase. SENCAR mice have been bred for their sensitivity to the promotion of skin tumors by phorbol esters whereas C57BL/6 mice have been shown to be resistant. When 12-O-tetradecanoylphorbol-13 acetate (TPA) was applied to the skin of SENCAR and C57BL/6 mice, SENCAR mice had a much more intense inflammatory response than the C57BL/6 animals. There was more edema formation at the site of application and vascular permeability was also greatly enhanced in the SENCAR strain. When samples of skin were examined microscopically, a fulminant, acute inflammatory cellular infiltrate was observed in SENCAR mice. Very few inflammatory cells migrated into the skin of C57BL/6 mice. At higher doses and multiple exposures to TPA there was a hyperplastic response of the keratinocytes in C57BL/6 mice, but it was less intense than in SENCAR mice. These data demonstrate that enhanced inflammatory responses in TPA in the skin correlate with the sensitivity to the promotion of skin tumors by TPA.