Effect of glutamine on tumor and host growth
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Background: Oral glutamine supplementation has been found to support gastrointestinal mucosal growth and increase intestinal and systemic toxicity after chemotherapy and radiation therapy. Glutamine is also an important nutrient for rapidly proliferating tumor cells. However, it is not clear whether long-term glutamine supplementation in the tumor-bearing host has a selective benefit for host growth or tumor cell proliferation.
Methods: To study the effect of glutamine in tumor-bearing animals, 30 Lewis/Wistar rats with subcutaneous mammary tumor implants (MAC-33) were randomized to receive a 3% glutamine- or 3% glycerine-enriched (control) diet for 25 days.
Results: No significant difference was found in carcass weight, primary tumor weight, or spontaneous pulmonary metastasis with glutamine supplementation. Tumor cell cycle kinetics (aneuploidy, %S and %S [synthetic] + G2/M [growth fraction]) were similar between glutamine-supplemented and control animals. A trophic effect of glutamine on distal ileal mucosa was seen with increased DNA content (344±68 vs. 184±38 µg/100 mg tissue) (p<0.05) and RNA content (435±44 VS. 335±30 µg/100 mg tissue) (p=0.06) compared with control animals. No detectable differences were observed in liver or muscle, or in tumor DNA, RNA, or protein content.
Conclusions: These findings confirm the trophic effect of glutamine on small intestinal mucosa and suggest that glutamine can be administered to the tumor-bearing host over a long period of time without significantly stimulating tumor growth kinetics or metastasis.
- Engstrom W, Zetterburg A. The relationship between purine, pyrimidine, nucleosides, and glutamine on the growth of human glioma and medulloblastoma.Cancer Res 1984;45:4077–4083.
- Fox AD, Kripke SA, DePaula J, Berman JM, Settle RE, Rombeau JL. Effect of a glutamine-supplemented enteral diet on methotrexate-induced enterocolitis.JPEN 1988;12:325–331.
- Klimberg V, Souba W, Dolson DJ. Oral glutamine supports crypt cell turnover and accelerates intestinal healing following abdominal radiation.JPEN 1989;13(suppl):11.
- Ziegler F, Bonneti F, Jardel A, et al. Glutamine-supplemented oral nutrition to restore the glutamine muscle pool in starved rats.Clin Nutr 1989;8(suppl):104–107.
- Hwang TL, O'Dwyer ST, Smith RJ. Preservation of the small bowel mucosa using glutamine-enriched parenteral nutrition.Surg Forum 1987;38:56–8.
- Souba WW, Strebel FR, Bull JM, Copeland EM, Teagtmeyer H, Cleary K. Interorgan glutamine metabolism in the tumor-bearing rat.J Surg Res 1988;44:720–726. CrossRef
- Chance WT, Cao L, Kim MW, Nelson JL, Fischer JE. Reduction of tumor growth following treatment with a glutamine antimetabolite.Life Sci 1988;42:87–94. CrossRef
- Klimberg VS, Souba W, Salloum RM, et al. Glutamine-enriched diet support muscle glutamine metabolism without stimulating tumor growth.J Surg Res 1990;48:319–323. CrossRef
- Austgen TR, Duorick PS, Sitren H, Bland KI, Copeland E, Souba WW. The effect of glutamine-enriched total parenteral nutrition on tumor growth and host tissues.Ann Surg 1992;215:117–113.
- Miller E, Czernobilsky B, Tsou KC. Mammary tumor induction after lymphoma in bred rats by dimethyl-B-aziridinoproprionamide.Am Soc Cancer Res 1976;8:182.
- Johnson FE, Laregina MC, Devine JE, Hudd C. Effect of chronically administered somatostatin on the nude mouse.J Surg Res 1986;40:346–352. CrossRef
- Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent.J Biol Chem 1951;193:265.
- Eagle H. Nutrition needs of mammalian cells in tissue culture.Science 1955;122:501–504.
- Newsholme EA, Parry-Billings M. Properties of glutamine release from muscle and its importance for the immune system.JPEN 1990;14(suppl):63–67.
- Ardawi MSM. Skeletal muscle glutamine production in terminally injured rats.Clin Sci 1988;74:165–172.
- Coles NW, Johnstone RM. Glutamine metabolism in Ehrlich ascites—carcinoma cells.Biochem J 1962;83:284–292.
- Kovacevic C, Morris HP. The role of glutamine in the oxidative metabolism of malignant cells.Cancer Res 1972;32:326–331.
- Kitoh T, Kubota M, Takimoto T, et al. Metabolic basis for differential glutamine requirements of human leukemia cell lines.J Cell Physiol 1990;143:150–153. CrossRef
- Brand K, Fekl W, Von Hintzenstern J, Langer K, Luppa P, Schoerner G. Metabolism of glutamine in lymphocytes.Metabolism 1989;38(suppl):29–33.
- Souba WW, Smith RJ, Wilmore DW. Glutamine metabolism by the intestinal tract.JPEN 1985;9(suppl):608–617.
- Matsuno T, Satoh T. Glutamine metabolism in the avian host bearing transplantable hepatomatous growth induced by MC-29 virus.Int J Biochem 1986;18:187–189.
- Marquez J, Sanchez-Jimenez F, Medina MA, Quesada AR, Nunez de Castro I. Nitrogen metabolism in tumor-bearing mice.Arch Biochem Biophys 1989;268:667–675. CrossRef
- Wu C, Gauer JM. A study of free amino acids and of glutamine synthesis in tumor-bearing rats.Cancer Res 1960;20:848–854.
- Quesada AR, Medina MA, Marquez J, Sanchez-Jimenez FM, Nunez de Castro I. Contribution by host tissues to circulating glutamine in mice inoculated with Ehrlich ascites tumor cells.Cancer Res 1988;48:1551–1553.
- Windmueller HG, Spaeth AE. Uptake and metabolism of plasma glutamine by the small intestine.J Biol Chem 1974;49:5070–5078.
- Bartlett DL, Charland S, Kalish E, Perkins M, Torosian MH. Somatostatin and insulin treatment for cancer cachexia.JPEN 1991;15(suppl):305.
- Souba WW, Herskowitz K, Salloum RM, Chen MK, Austgen TR. Gut glutamine metabolism.JPEN 1990;14(suppl):45–50.
- Souba WW, Klimboff VS, Hautamaki RO, et al. Oral glutamine reduces bacterial translocation following abdominal radiation.J Surg Res 1990;48:1–5.
- Scheltinga MR, Young LS, Benfell K, et al. Glutamine-enriched intravenous feedings attenuate extracellular fluid expansion after a standard stress.Ann Surg 1991;214:385–395.
- Ziegler TR, Young LS, Benfell K, et al. Clinical and metabolic efficacy of glutamine-supplemented parenteral nutrition after bone marrow transplantation.Ann Intern Med 1992;116:821–828.
- Effect of glutamine on tumor and host growth
Annals of Surgical Oncology
Volume 2, Issue 1 , pp 71-76
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- 1. From the Department of Surgery and Harrison Department of Surgical Research, University of Pennsylvania School of Medicine, and the Veterans Administration Medical Center, Philadelphia, Pennsylvania, USA