Polyamine-directed preferential nutritional repletion of normal tissues in tumor-bearing hosts

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Abstract
Our previous study demonstrated that total parenteral nutrition (TPN) increases erythrocyte (RBC) polyamines selectively in cancer patients but not in non-cancer patients, suggesting that these changes may relate to tumor presence. We therefore studied the possible relationship between RBC polyamine levels and potential tumor growth induced by TPN. In addition, we attempted to control tumor growth during TPN with α-difluoromethylornithine (DFMO), a suicide inhibitor of ornithine decarboxylase (ODC), in a fibrosarcoma-bearing rat model. Rats in a control group received chow ad libitum for 3 weeks and their tumors grew exponentially. A restricted intake (RI) tumor-bearing group received 8 g chow per day per rat; this produced malnourished rats in which tumor growth significantly slowed. The third group (RI → TPN) received the RI diet for 2 weeks and TPN for 1 week, which resulted in an increase in tumor growth. The last group (RI → TPN + DFMO) received a 2-week RI regimen and 1-week TPN plus DFMO regimen, which inhibited tumor growth to the level of the RI group due to the addition of DFMO (1 g/kg/day). Although the addition of TPN to the RI regimen markedly increased tumor ODC activity, as well as tumor putrescine and RBC putrescine levels, the addition of DFMO to the RI → TPN regimen entirely abolished these increases. Despite DFMO treatment, liver ODC activity in RI → TPN + DFMO group was unaffected. The plasma albumin level, an indicator of host nutrition, of the RI → TPN + DFMO group was significantly higher than that of the RI group. Liver, spleen, kidney and total body weights of the RI → TPN or RI → TPN + DFMO group were significantly higher than those of the RI group. These results indicate that TPN can enhance tumor growth in malnourished hosts and that the addition of DFMO to TPN can effectively control this TPN-enhanced tumor growth, leading to preferential nutritional repletion of the host.