Substituting ornithine for arginine in total parenteral nutrition eliminates enhanced tumor growth.

Total parenteral nutrition (TPN) may enhance the growth of some tumors: this enhanced growth is associated with an increase in the erythrocyte polyamine levels. The effect of arginine in TPN on tumor growth was compared with ornithine using rats with a transplantable Ward colon tumor. The relationship of circulating arginine, ornithine, glutamine, and polyamines with tumor growth was investigated. For rats fed chow ad libitum, increasing tumor weights were associated with a linear decrease in the plasma arginine levels which was consistently lower than that of age-matched non-tumor bearing (NTB) rats; ornithine and lysine levels were not affected. Subsequent experiments suggest that plasma glutamine levels were also lower in tumor bearing rats. Pair-fed NTB rats had reduced arginine but not glutamine levels in plasma. TPN regimens with arginine or with ornithine substituted for arginine at two levels (equimolar [Orn-Em] or isonitrogenous [Orn-IN]) were given to colon tumor bearing rats for 8 days. The final tumor weight of rats which received the arginine-containing regimen (19.8 +/- 5.7 g, n = 4) (P less than 0.05) was significantly greater than the tumor weight of rats fed chow ad libitum (12.1 +/- 3.3 g, n = 6). The final tumor weights of Orn-EM (11.2 +/- 2.6 g, n = 4) or Orn-IN (11.6 +/- 0.8 g, n = 6) were similar to the chow-fed controls. The plasma arginine levels were elevated, compared with the control, when arginine was present in the regimen. The plasma arginine levels of rats which received Orn-EM or Orn-IN were lower than the controls. The plasma ornithine levels were not affected by arginine in the regimen but were elevated with increasing levels of ornithine in TPN. Plasma glutamine levels were decreased when arginine was present in the regimen but were elevated when ornithine was substituted for arginine. Erythrocyte putrescine was increased when either arginine or ornithine was included in the TPN regimens. These results demonstrate that while arginine in a parenteral regimen stimulates tumor growth, substituting ornithine for arginine in TPN does not enhance the growth of a transplantable colon tumor.

Duke Scholars

Author David Masao Ota Surgical Oncology