March 1974
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17 Reads
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23 Citations
Cancer Research
A new enzyme termed GA:1.2, possessing approximately equal amounts of glutaminase and asparaginase activity, has antitumor activities against cancers other than leukemia, thus enlarging the potential for cancer therapy by amino acid deprivation. When tested against the asparagine dependent EARAD 1 leukemia in the presence of the lactate dehydrogenase elevating virus (LDH virus), striking tumor regression was obtained. This asparagine dependent mouse tumor was used as a model to study the basic mechanism of the therapeutic action of the enzyme and its influence upon various plasma amino acids in the presence and absence of the LDH virus. At doses of 150 IU/kg and higher, both plasma glutamine and asparagine were depleted to undetectable levels (less than 1 nmole/ml) when the virus was present, but not in its absence. Tumor regression was correlated with asparagine and glutamine depletion in the plasma. Although there were no measurable differences in the plasma glutamine and asparagine depletion below 1 nmole/ml as a function of increasing enzyme dose, both glutamic and aspartic acids increased systematically with dose. The plasma half life of GA:1.2 is 1 to 2 hr in normal mice, but was increased to 12 to 18 hr when mice were infected with the LDH virus. Thus, the presence of the LDH virus in the host is necessary for the expression of the therapeutic capabilities of the enzyme preparation on this and presumably other mouse tumor systems.