Neomycin inhibition of intestinal putrescine uptake.
Enhanced intestinal polyamine uptake was confirmed in tumor-bearing rats. Intestinal brush border membrane from rats bearing a Mat Lylu prostatic adenocarcinoma exhibited 46% increase in 14C putrescine uptake. After oral ingestion of 14C putrescine, radioactivity was recovered in the tumor (about 2% of total amount ingested) and was enhanced in liver and in blood. Radioactivity in tumor-bearing rat red blood cells (RBC) was two-fold higher than in healthy control rats indicating that polyamines originating in food can contribute to the enhancement of RBC polyamine levels observed after tumor development. Neomycin-induced inhibition of intestinal putrescine absorption was observed both in vitro and in vivo. In intestinal brush border membrane 500 microM neomycin inhibited putrescine uptake by 30-35%. In vivo, a single dose of neomycin given per os modified final 14C radioactivity distribution: a) The final accumulation of radioactivity in the tumor was reduced by 50%. b) Neomycin treatment lowered the high levels of radioactivity in the blood of cancerous animals. This reduction was correlated with a significant reduction of RBC polyamine levels. c) Radioactivity accumulated in the colon after neomycin treatment in both healthy and cancerous rats. The role of neomycin as an intestinal antibiotic and the presently described effect of this drug on intestinal polyamine uptake emphasize the importance of neomycin in polyamine deprivation treatments.
Hardy
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A
Laboratoire de Biologie Cellulaire, UPRES-A CNRS 6027, Faculté de Médecine de Rennes, France.
Catros-Quemener
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V
D000230:Adenocarcinoma / Q000097:blood / Q000378:metabolism*; D000284:Administration, Oral; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002250:Carbon Radioisotopes; D003106:Colon / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism*; D009355:Neomycin / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000097:blood / Q000378:metabolism*; D011700:Putrescine / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D012016:Reference Values; D013095:Spermidine / Q000378:metabolism; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D009355:Neomycin; D013095:Spermidine; D011700:Putrescine