POLYAMINE METABOLISM AS TARGET FOR CANCER CHEMOPREVENTION

The natural polyamines putrescine, spermidine and spermine are intimat ely involved in growth-related processes. More and more evidence indic ates that the excessive accumulation of putrescine and spermidine favo rs malignant transformation of cells. Selective depletion of putrescin e has been shown to restore in some transformed cells the normal pheno type. Inhibition of polyamine formation appears, therefore, a rational target in chemoprevention. Clinical trials with 2-(difluoromethyl)orn ithine, a selective inactivator of ornithine decarboxylase, a key enzy me of polyamine biosynthesis, are promising. Structural analogs of the polyamines with polyamine-mimetic or antagonist properties, and calmo dulin antagonists are other types of drugs which affect several key re actions of polyamine metabolism and appear to be candidates for the pr evention of carcinogenesis especially of the,gastrointestinal tract.