Epidermal Cell Proliferation and Promoting Ability of Phorbol Esters2

Abstract

Dose-response relationships on the abilities of several phorbol ester tumor promoters to promote skin tumors after 7,12-dimethylbenz[a]anthracene initiation and to bring about edema, inflammation, and epidermal hyperplasia were determined in female Charles River CD-1 mice. The promoting ability of the potent synthetic promoter, phorbol-12,13-dioctanoate (PdiC₈), was determined over a dose range of 0.1–10 µg/application. Administration of PdiC₈ two times weekly at dosages of 4, 6, 8, and 10 µg gave little variation in tumor response. A dose-dependent tumor response occurred at doses of 1–4 µg PdiC₈. Only 1 papilloma was observed when PdiC₈ was given twice weekly at a dose of 0.1 or 0.5 µg. A similar dose-response relation was observed for the ability of PdiC₈ to stimulate epidermal hyperplasia. Investigations of other phorbol esters revealed an excellent correlation between their promoting ability and their ability to induce epidermal hyperplasia; however, that was not the case for compounds outside the phorbol ester series (i.e., acetic acid, cantharidin, and ethylphenylpropiolate).