INVOLVEMENT OF POLYAMINES IN TUMOR-GROWTH - ANTITUMORAL EFFECTS OF POLYAMINE DEPRIVATION

The fact that tumors require polyamines for growth has been repeatedly demonstrated. In vivo polyamines are available both from endogenous ( intracellular biosynthesis) and exogenous sources (food and intestinal microflora). We investigated in rats grafted with Mat-Lylu prostatic adenocarcinoma the distribution between tumor and tissues of orally ad ministered (C-14) putrescine (Pt). The amount of radioactivity retaine d by tumors was directly proportional to the tumor volume. In a tumor of 25 cm(3) 19% of the totally retained radioactivity was found. The a ccumulation of Pt by intestinal brush-border membrane vesicles prepare d from tumor-bearing animals was significantly higher than by vesicles from healthy rats. Our results indicate that the presence of a tumor induces an adaptive response in the small intestine which stimulates t he uptake of exogenous polyamines. Our therapeutic strategy was to rea lise a total blockade of all endogenous and exogenous sources of polya mines by feeding animals with a drug (DEMO, MDL 72527, antibiotics) co ntaining polyamine deficient chow. We observed that polyamine deprivat ion largely reduced both primary tumor and metastatic development. Nat ural Killer cell cytotoxic activity and blood formula were restored to normal values after treatment. Furthermore polyamine deprivation enha nced antitumoral efficacy of chemotherapy.