Tumor Glutamine Level Is Negatively Correlated with Tumor Weight in Tumor-Bearing Rats Administered a Glutamine Antagonist and a New Imbalanced Amino Acid Solution.

Abstract

We examined the anti-tumor capacity and alterations of glutamine metabolism in tumor-bearing rats by administering a combination of a glutamine antagonist and total parenteral nutrition with an imbalanced solution of amino acids. Rats inoculated with Yoshida sarcoma were divided into two groups: group I (n=11) received a solution enriched in branched-chain amino acids, while group II (n=10) was deprived of non-essential amino acids. Both groups received a glutamine antagonist (6-diazo-5-oxo-L-norleucine) given 7 days after tumor inoculation. Tumor weight in group II was significantly lower than that in group I. The relationship between tumor weight and levels of free amino acids in tumor tissue showed a negative correlation with many amino acids, with the highest observed for glutamine. And this correlation was apparent in group II, but not in group I, suggesting that glutamine utilization by the tumor was inhibited to a greater extent in group II. These data suggest that complete inhibition of glutamine utilization by Yoshida sarcoma may lead to a marked reduction in tumor growth, because of its characteristic dependence on glutamine.