EFFECT OF GLUTAMINE AND CHEMOTHERAPY ON PROTEIN-METABOLISM IN TUMOR-BEARING RATS

Supplemental glutamine prevents gut atrophy and enhances muscle protein synthesis in septic rats. This study investigated the effect of glutamine administration and mitomycin C treatment on protein turnover in tumor-bearing rats. AH109A rat ascites hepatoma cells (2 X 10(6)) were subcutaneously implanted in the back of male Donryu rats (n = 32, body weight 150-200 g) on Day 0. The animals were then fed rat chow ad libitum for 10 days. On Day 10, the rats were catheterized for TPN and randomized into four groups according to diet and treatment. The groups were: (i) standard total parenteral nutrition (STPN) + saline; (ii) glutamine-supplemented TPN (GTPN) + saline; (iii) STPN + mitomycin C (MMC); (iv) GTPN + MMC. GTPN was isocaloric (250 kcal/kg/day) and isonitrogenous (1.5 gN/kg/day) with STPN. The animals were maintained on TPN for 5 days and received mitomycin C (0.5 mg/kg) via the catheter every day. On the fifth day of TPN, [1-C-14]leucine was given via a 5-hr continuous infusion (2.0 mu Ci/hr/rat) to determine the fractional synthesis rate of muscle, gut mucosa, liver, and tumor. Also, endogenous leucine production (edqual-sign-with-dot-above-and-below whole body protein breakdown rate) was calculated. Body weight loss during TPN was reduced with GTPN. GTPN enhanced muscle FSR in untreated animals (STPN: 10.8 +/- 8.7%/day vs GTPN: 14.7 +/- 0.6%/day, P < 0.05) and in mitomycin C-treated animals (STPN + MMC: 9.6 +/- 0.9%/day, GTPN + MMC: 12.0 +/- 0.8%/day, P < 0.05). The whole body protein breakdown rate was reduced with GTPN. Mitomycin C reduced the mucosal fractional synthesis rate and GTPN did not prevent this reduction. There was no effect of glutamine on tumor protein synthesis. These results showed that glutamine supplementation improved nitrogen retention in tumor-bearing rats during chemotherapy without enhancing tumor growth. (C) 1994 Academic Press, Inc.