A reinvestigation of epidermal transplantation during chemical carcinogenesis.

The possibility that epidermis which has never been exposed to carcinogen can give rise to carcinomas if it is transplanted onto carcinogen-treated dermis was raised by the experiment reported by Billingham, Orr, and Woodhouse in 1951. They treated mice topically with methylcholanthrene for 12 weeks, left them untreated for 2 weeks to allow the methylcholanthrene to disappear, and then transplanted autografts of untreated epidermis obtained by trypsinization of tail skin to superficial beds prepared in the treated areas on the thorax. Tumors apparently developed from the untreated surface epidermis at 62% of the graft sites. However, in preparation of the graft beds the bases of surviving hair follicles were left in situ. Consequently, it was possible that the tumors arose from residual treated epithelium and not from the untreated epidermal grafts. To test this possibility, the original experiment was repeated in the present investigation except that F! hybrid mice were used as the methylcholanthrene-treated hosts and inbred parent strain mice as the donors of the untreated epidermal grafts. This provided a strong (H-2) histocompatibility marker for determining the origin of the tumors by their differential transplantability to preimmunized parent strain versus F! hybrid recipients. Of 14 carcinomas which arose at the graft sites in the primary hosts, none grew progressively in the parent strain whereas all grew in the F] hybrids indicating that they indeed arose from F! host cells. These results suggest that the interpretation of the original experiment as evidence of indirect epidermal carcinogenesis is incorrect.