Inhibition of tumor promotion by DL-alpha-difluoromethylornithine, a specific irreversible inhibitor of ornithine decarboxylase.
Knowledge of the mechanisms of carcinogenesis is helpful for planning strategies and in the rational choice of agents for cancer prevention. There is a great potential for intervention at the promotion step of human carcinogenesis. ODC induction is associated with the promotion stage of carcinogenesis. Consequently, DFMO may be a useful drug for cancer prevention in humans. Long-term medication with higher doses (9 gm/m2/da) of DFMO has resulted in several toxic side effects, such as thrombocytopenia and reversible ototoxicity. However, doses of DFMO (less than 1 gm/m2/da), selected by our in vitro human skin punch biopsy assay (16, 47), may be given for a longer period without appreciable toxicity and should be evaluated in human cancer prevention trials.
Verma
A K
AK
Department of Human Oncology, University of Wisconsin Clinical Cancer Center, Madison 53792.
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000517:prevention & control; D000518:Eflornithine / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control; D051379:Mice; D009955:Ornithine Decarboxylase / Q000378:metabolism; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000378:metabolism; D051381:Rats; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity
D002273:Carcinogens; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate; D000518:Eflornithine