Inhibition of tumor promotion by DL-alpha-difluoromethylornithine, a specific irreversible inhibitor of ornithine decarboxylase

Basic Life Sci. 1990;52:195-204. doi: 10.1007/978-1-4615-9561-8_16.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Carcinogens / toxicity*
  • Colonic Neoplasms / chemically induced
  • Colonic Neoplasms / prevention & control
  • Eflornithine / pharmacology
  • Eflornithine / therapeutic use*
  • Female
  • Mammary Neoplasms, Experimental / chemically induced
  • Mammary Neoplasms, Experimental / prevention & control
  • Mice
  • Ornithine Decarboxylase / metabolism
  • Ornithine Decarboxylase Inhibitors*
  • Polyamines / metabolism
  • Rats
  • Skin Neoplasms / chemically induced
  • Skin Neoplasms / prevention & control
  • Tetradecanoylphorbol Acetate / toxicity

Substances

  • Carcinogens
  • Ornithine Decarboxylase Inhibitors
  • Polyamines
  • Ornithine Decarboxylase
  • Tetradecanoylphorbol Acetate
  • Eflornithine