[The involvement of polyamines in the malignant proliferative process. The anticancer effect 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 administered (14C) putrescine (Pt). The amount of radioactivity retained by tumors was directly proportional to the tumor volume. In a tumor of 25 cm3 19% of the totally retained radioactivity was found. The accumulation of Pt by intestinal brush-border membrane vesicles prepared 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 the uptake of exogenous polyamines. Our therapeutic strategy was to realise a total blockade of all endogenous and exogenous sources of polyamines by feeding animals with a drug (DFMO, MDL 72527, antibiotics) containing polyamine deficient chow. We observed that polyamine deprivation largely reduced both primary tumor and metastatic development. Natural Killer cell cytotoxic activity and blood formula were restored to normal values after treatment. Furthermore polyamine deprivation enhanced anti-tumoral efficacy of chemotherapy.
Quemener
V
V
Laboratoire de Biologie Cellulaire, GRETAC, URA CNRS 1529, CHU, Rennes.
Chamaillard
L
L
Brachet
P
P
Havouis
R
R
Moulinoux
J P
JP
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control* / Q000556:secondary; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001773:Blood Cells / Q000187:drug effects; D002250:Carbon Radioisotopes; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D004357:Drug Synergism; D000518:Eflornithine / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000187:drug effects; D008175:Lung Neoplasms; D008297:Male; D008795:Metronidazole / Q000627:therapeutic use; D051379:Mice; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D009355:Neomycin / Q000627:therapeutic use; D009368:Neoplasm Transplantation; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000037:antagonists & inhibitors; D011471:Prostatic Neoplasms; D011700:Putrescine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains
D000970:Antineoplastic Agents; D002250:Carbon Radioisotopes; D008795:Metronidazole; C044445:MDL 72527; D000587:Oxidoreductases Acting on CH-NH Group Donors; D009355:Neomycin; D011700:Putrescine; D000518:Eflornithine
Implication des polyamines dans les processus prolifératifs malins. Effets anticancéreux d'une carence en polyamines.