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Amino Acids of the 6C3HED Lymphosarcoma following Treatment with Asparaginase

University of Nebraska College of Medicine, Omaha, Nebraska 68105

The mechanism by which asparaginase inhibits the 6C3HED tumor is probably not directly related to the cellular concentration of asparagine, since the concentration of asparagine decreases in resistant tumors, spleen, and liver, as well as in susceptible tumors. Amino acids other than asparagine may be affected by asparaginase because of the variety of metabolic relationships of the amino acids. In this study, analyses of all the amino acids of resistant 6C3HED tumor, susceptible 6C3HED tumor, spleen, and liver were undertaken.

Most of the amino acids of the susceptible tumor increased from 2- to 40-fold, while only slight changes occurred in the resistant tumor. The most dramatic change was a decrease in glycine in the susceptible tumor. No parallel change in glycine occurred in the resistant tumor, the spleen, or the liver. It is suggested that the susceptible tumor may synthesize glycine from asparagine; consequently, the decrease in asparagine is followed by a decrease in cellular glycine. The resistant tumor, the spleen, and the liver may obtain glycine from an alternate metabolic route.

Received 6/23/69. Accepted 9/24/69.