Effects of complete and incomplete tumor promoters on hair growth, angiogenesis, and tenascin expression in the skin of NMRI mice.

Although the phorbol esters 12-O-tetradecanoylphorbol-13-acetate (TPA) and 12-O-retinoylphorbol-13-acetate (RPA) are almost equipotent inducers of an inflammatory and hyperplastic response in NMRI mouse skin, TPA acts as a converting or complete and RPA as a non-converting or incomplete skin tumor promoter. Bearing in mind the converting effect of skin wounding and TGF beta, we have addressed the question of a relationship between conversion and stromal events. For this purpose we have compared the effects of TPA and RPA on dermal angiogenesis, hair regrowth and the expression of tenascin in NMRI mouse skin in vivo. In the reticular part of the dermis, shaving alone induced angiogenesis peaking at day 14, concomitant with hair regrowth. While TPA exhibited a stimulatory effect on both parameters, RPA suppressed shaving-induced angiogenesis and delayed the onset of hair regrowth. Whether this difference in the phorbol ester effects being consistent with the working hypothesis is critical for conversion, remains to be shown. In the papillary dermis, however, RPA was more potent than TPA in inducing vascularization and tenascin expression. The kinetics of both responses corresponded to the time course of hyperproliferation induced by the phorbol esters in the overlaying epidermis, i.e. may be related to promotion proper, rather than conversion.