The role of prostaglandin E1 in ornithine decarboxylase induction by tumor promoters.

The effect of topical application of PGE on induction of ODC in mouse epidermis was measured. When direct induction of ODC by TPA was blocked by also applying indomethacin, maximum ODC activity occurred only when PGE was applied simultaneously with TPA 4 1/2 hr before killing of the mice. If either TPA or PGE was applied at other times, ODC activity decreased substantially. Induction of ODC by mezerein was blocked by indomethacin but restored by PGE, as was observed with TPA, but induction by ethyl phenylpropiolate was not affected by indomethacin or PGE. DMBA did not cause a consistent increase in ODC activity, nor was its inductive action affected by indomethacin or PGE. However, another weak inducer, acetic acid, exhibited elevated ODC activity when PGE was also applied. Inhibition by topical retinoic acid of ODC induction by TPA was partially overcome in a dose-response fashion by PGE. The results indicate that at least 2 events, elevation of PGE and another independent event, are required for induction of ODC activity. It appears that TPA causes at least 4 independent events essential for tumor promotion. A model for the events in the 2-stage tumor promotion model is proposed.