Evidence that the epidermal targets of carcinogen action are found in the interfollicular epidermis or infundibulum as well as in the hair follicles

Actively cycling, transit-amplifying cells and quiescent cells including stem cells are found in the layer of the epidermis and hair follicles. To determine the origin of skin tumors, we completely removed the interfollicular epidermis of carcinogen-initiated mice by an abrasion technique known to leave the hair follicles undisturbed. The interfollicular epidermis of the abraded mice quickly regenerated from cells in the hair follicles, after which time tumor promotion was begun. Mice in which the interfollicular epidermis had been removed developed papillomas and carcinomas; however, the number of papillomas throughout 40 weeks was half that of the unabraded mice. Carcinoma responses were not significantly different in the abraded and unabraded groups. These results are consistent with the hypothesis that the targets of tumor initiation are stem cells found in the hair follicles and, to a lesser degree, in the interfollicular epidermis.