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

Involvement of polyamines in tumor growth : antitumoral effects of pol yamine deprivation. The fact that tumors require polyamines for growth has been repeatedly demonstrated. In vivo polyamines are available bo th 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 administered [C-14]putrescine (Pt). The amount of ra dioactivity retained by tumors was directly proportional to the tumor volume. In a tumor of 25 cm(3) 19 % of the totally retained radioactiv ity was found. The accumulation of Pt by intestinal brush-border membr ane vesicles prepared from tumor-bearing animals was significantly hig her than by vesicles from healthy rats. Our results indicate that the presence of a tumor induces an adaptive response in the small intestin e which stimulates the uptake of exogenous polyamines. Our therapeutic strategy was to realise a total blockade of all endogenous and exogen ous sources of polyamines by feeding animals with a drug (DFMO, MDL 72 527, antibiotics) containing polyamine deficient chow. We observed tha t polyamine deprivation largely reduced both primary tumor and metasta tic development. Natural Killer cell cytotoxic activity and blood form ula were restored to normal values after treatment. Furthermore polyam ine deprivation enhanced antitumoral efficacy of chemotherapy.