Effect of phorbol esters on guniea pig skin in vivo.

When topically applied to guniea pig ear skin the tumor promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) induced inflammation and epidermal hyperproliferation which could be inhibited by indomethacin. This inhibition could be reversed both by prostaglandins E and F. Five minutes after TPA treatment an increase in the level of prostaglandin E but not of prostaglandin F was observed in the epidermis. The non-promoting phorbol ester 4-O-methyl-TPA also stimulated epidermal cell proliferation but this stimulation was not inhibited by indomethacin. The above results are in agreement with those already reported in the mouse system with these two compounds. Ornithine decarboxylase (ODC) activity has been evaluated in the epidermis of guniea pig ear after topical application of 20 nmol of TPA. No increase was noted. This is in contrast with the well documented activation of ODC in mouse skin treated with TPA. Since TPA acts as a promoter in the mouse whereas both croton oil and TPA have no promoting action in the guinea pig, the above result supports the view that ODC activationis related to promotion, and provides a possible explanation for the resistance of this animal species to promotion. This resistance is further documented by the fact that no "dark cells" were found in guinea pig ear skin.