12-o-retinoylphorbol-13-acetate and Hyperplasia

Hyperplasiogenic and tumor-promoting phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate or 12-O-retinoylphorbol-13-acetate induce the sequential transient expression of the proto-oncogenes c-fos and c-myc and the ornithine decarboxylase gene in mouse skin in vivo. This sequence of biochemical events probably depends on an activation of protein kinase C by these agents. The non-irritant skin mitogens 4-O-methyl-12-O-tetradecanoylphorbol-13-acetate and ethyl phenyl propiolate do not increase the expression of these genes to a comparable extent. Thus, 12-O-tetradecanoylphorbol-13-acetate and 12-O-retinoylphorbol-13-acetate induce epidermal hyperproliferation by different biochemical mechanisms as do 4-O-methyl-12-O-tetradecanoylphorbol-13-acetate and ethylphenylpropiolate.

Topics: Animals; Female; Hyperplasia; Mice; Ornithine Decarboxylase; Phorbol Esters; Proto-Oncogenes; RNA, Messenger; Skin; Tetradecanoylphorbol Acetate

By means of a two-stage promotion protocol in mouse epidermis with 12-O-tetradecanoylphorbol-13-acetate as first-stage promoter and 12-O-retinoylphorbol-13-acetate as second-stage promoter, the effects of the former that are critical and obligatory for tumor promotion were shown to be irreversible in nature for at least 8 weeks. The reversibility of tumor promotion was related to the second stage of promotion, reflecting the reversibility of epidermal hyperplasia induced by 12-O-tetradecanoylphorbol-13-acetate.

Topics: Animals; Carcinogens; Cell Line; Epidermis; Female; Hyperplasia; Mice; Mice, Inbred Strains; Neoplasms, Experimental; Phorbol Esters; Phorbols; Precancerous Conditions; Skin Neoplasms; Tetradecanoylphorbol Acetate; Time Factors