Induction of the polyamine-biosynthetic enzymes in mouse epidermis by tumor-promoting agents

Abstract

A single topical application of 1.0 mg of crotol oil or 17 nmoles of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) resulted in a rapid, transient stimulation of mouse epidermal ornithine decarboxylase activity. The activity reached a peak (230-fold greater than control after TPA) at 4 to 5 hr after croton oil or TPA treatment and returned to control level by 12 hr. The stimulation of S-adenosyl-L-methionine decarboxylase activity was less pronounced, reaching a peak of activity (6- to 7-fold greater than control) at 9 to 12 hr after TPA or croton oil and slowly declining to control level. The stimulation of both enzyme activities was dependent on the dose of TPA applied and correlated well with the promoting ability of these doses on mouse skin. Phorbol, the nonpromoting parent alcohol of TPA, did not affect the enzymes activities. Cycloheximide pretreatment abolished the increase in enzyme activities after TPA application. By measuring the decline of enzyme activity following cycloheximide treatment, enzyme half-lives of 17 and 41 min were obtained for ornithine and S-adenosyl-L-methionine decarboxylase, respectively. 5-Azacytidine pretreatment prevented the stimulation of enzyme activities by TPA, while actinomycin D had no effect. Cordycepin (3'-deoxyadenosine) partially blocked the rise in enzyme activities.