Polyamine deprivation, malnutrition and tumor growth

Feeding an artificial, essentially polyamine-free diet which contained antibiotics for the decontamination of the gastrointestinal tract and 2-(difluoromethyl)ornithine (DFMO) and N,N'-bis-(2,3-butadienyl)putrescine for the inactivation of ornithine decarboxylase and polyamine oxidase, respectively, retarded the growth of several solid tumors by about 80%. In the present work the contribution of the major components of the treatment were analysed, using Lewis lung carcinoma growing in the hind leg of female C57BL mice. In addition to polyamine deprivation, malnutrition due to decreased food intake turned out to contribute significantly to tumor growth retardation. Ornithine decarboxylase was shown to be incompletely inhibited by administration of DFMO with the diet. A considerable improvement of polyamine deprivation can be expected from the continuous administration of this drug, or from analogous inhibitors with more favourable enzyme- and pharmaco-kinetic properties.