Skip to main content
SpringerLink
Log in

Effect of glutamine on tumor and host growth

  • Original Articles
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. 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.

    Google Scholar 

  2. 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.

    CAS  Google Scholar 

  3. Klimberg V, Souba W, Dolson DJ. Oral glutamine supports crypt cell turnover and accelerates intestinal healing following abdominal radiation.JPEN 1989;13(suppl):11.

    Google Scholar 

  4. 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.

    Google Scholar 

  5. Hwang TL, O'Dwyer ST, Smith RJ. Preservation of the small bowel mucosa using glutamine-enriched parenteral nutrition.Surg Forum 1987;38:56–8.

    Google Scholar 

  6. 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.

    Article  CAS  PubMed  Google Scholar 

  7. 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.

    Article  CAS  PubMed  Google Scholar 

  8. 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.

    Article  CAS  PubMed  Google Scholar 

  9. 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.

    Google Scholar 

  10. 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.

    Google Scholar 

  11. Johnson FE, Laregina MC, Devine JE, Hudd C. Effect of chronically administered somatostatin on the nude mouse.J Surg Res 1986;40:346–352.

    Article  CAS  PubMed  Google Scholar 

  12. Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent.J Biol Chem 1951;193:265.

    CAS  PubMed  Google Scholar 

  13. Eagle H. Nutrition needs of mammalian cells in tissue culture.Science 1955;122:501–504.

    CAS  PubMed  Google Scholar 

  14. Newsholme EA, Parry-Billings M. Properties of glutamine release from muscle and its importance for the immune system.JPEN 1990;14(suppl):63–67.

    Google Scholar 

  15. Ardawi MSM. Skeletal muscle glutamine production in terminally injured rats.Clin Sci 1988;74:165–172.

    CAS  PubMed  Google Scholar 

  16. Coles NW, Johnstone RM. Glutamine metabolism in Ehrlich ascites—carcinoma cells.Biochem J 1962;83:284–292.

    CAS  PubMed  Google Scholar 

  17. Kovacevic C, Morris HP. The role of glutamine in the oxidative metabolism of malignant cells.Cancer Res 1972;32:326–331.

    CAS  PubMed  Google Scholar 

  18. 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.

    Article  CAS  PubMed  Google Scholar 

  19. Brand K, Fekl W, Von Hintzenstern J, Langer K, Luppa P, Schoerner G. Metabolism of glutamine in lymphocytes.Metabolism 1989;38(suppl):29–33.

    CAS  PubMed  Google Scholar 

  20. Souba WW, Smith RJ, Wilmore DW. Glutamine metabolism by the intestinal tract.JPEN 1985;9(suppl):608–617.

    CAS  Google Scholar 

  21. 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.

    CAS  PubMed  Google Scholar 

  22. 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.

    Article  CAS  PubMed  Google Scholar 

  23. Wu C, Gauer JM. A study of free amino acids and of glutamine synthesis in tumor-bearing rats.Cancer Res 1960;20:848–854.

    CAS  PubMed  Google Scholar 

  24. 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.

    CAS  PubMed  Google Scholar 

  25. Windmueller HG, Spaeth AE. Uptake and metabolism of plasma glutamine by the small intestine.J Biol Chem 1974;49:5070–5078.

    Google Scholar 

  26. Bartlett DL, Charland S, Kalish E, Perkins M, Torosian MH. Somatostatin and insulin treatment for cancer cachexia.JPEN 1991;15(suppl):305.

    Google Scholar 

  27. Souba WW, Herskowitz K, Salloum RM, Chen MK, Austgen TR. Gut glutamine metabolism.JPEN 1990;14(suppl):45–50.

    Google Scholar 

  28. Souba WW, Klimboff VS, Hautamaki RO, et al. Oral glutamine reduces bacterial translocation following abdominal radiation.J Surg Res 1990;48:1–5.

    CAS  PubMed  Google Scholar 

  29. 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.

    CAS  PubMed  Google Scholar 

  30. 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.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  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

    David L. Bartlett MD, Scott Charland PharmD &  Michael H. Torosian MD

Authors
  1. David L. Bartlett MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Scott Charland PharmD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael H. Torosian MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bartlett, D.L., Charland, S. & Torosian, M.H. Effect of glutamine on tumor and host growth. Annals of Surgical Oncology 2, 71–76 (1995). https://doi.org/10.1007/BF02303705

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02303705

Key Words

Search

Navigation