Abstract
dl-α-Difluoromethylornithine (DFMO) is an enzyme-activated irreversible inhibitor of mammalian ornithine decarboxylase. DFMO, when administered in drinking water, precludes increases in the levels of intracellular putrescine and spermidine and also inhibits the induction of skin, breast, colon, urinary bladder, and intestinal cancers in experimental animal models. DFMO may be a useful drug for cancer prevention in humans; however, long-term medication with higher doses (9 g/m 2/day) of DFMO has resulted in several toxic side effects such as thrombocytopenia and reversible ototoxicity. Smaller doses (<1 g/m 2/day), selected by our in vitro human skin punch biopsy assay, may be given for a longer period without appreciable toxicity. Further evaluation in human cancer prevention trials is indicated.
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