Dose and schedule of oral retinoic acid and indomethacin needed to effectively inhibit phorbol ester-induced epidermal ornithine decarboxylase activity

Currently there is no well-defined biological parameter or marker to help define agents, doses, and dose schedules for human cancer chemoprevention trials. Induction of ornithine decarboxylase, the rate limiting enzyme in the polyamine biosynthetic pathway, has been shown to be an essential aspect of mouse skin tumor promotion. Supplementary information suggest that this enzyme is an important aspect of carcinogenesis in other organ systems and in other animals (including humans). We have developed an assay system which effectively measured tumor promoter (TPA)-induced ornithine decarboxylase activity on 3-4 mm skin samples from mice and humans. Using this system we evaluated the doses and dose schedules of retinoic acid and indomethacin needed to effectively inhibit ornithine decarboxylase activity. Our data suggest that the doses and schedules of these compounds needed to inhibit ornithine decarboxylase activity would be toxic in humans.