EFFECT OF GLUTAMINE ON TUMOR AND HOST GROWTH

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] + G(2)/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 mu g/100 mg tissue) (p < 0.05) and RNA content (435 +/- 44 vs. 335 +/- 30 mu g/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.