Inhibition of ornithine decarboxylase activity by small doses of alpha-difluoromethylornithine.
The induction of ornithine decarboxylase (ODC) appears to be an important aspect of carcinogenesis. Agents which inhibit ODC have been shown to preclude cancer formation in many organ systems. We studied the dose and dose schedule of alpha-difluoromethylornithine (DFMO), a suicide inhibitor of ODC, needed to effectively inhibit ODC activity in mice. Our data demonstrate that doses many-fold lower than comparable maximal tolerated doses in humans can inhibit ODC activity in mice. In addition, a simplified, once daily dosage of DFMO appears adequate.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D000518:Eflornithine; D007668:Kidney / Q000201:enzymology; D051379:Mice; D009952:Ornithine / Q000031:analogs & derivatives* / Q000494:pharmacology; D065108:Ornithine Decarboxylase Inhibitors; D012867:Skin / Q000201:enzymology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D065108:Ornithine Decarboxylase Inhibitors; D009952:Ornithine; D013755:Tetradecanoylphorbol Acetate; D000518:Eflornithine