FREE AMINO ACIDS IN BLOOD. I B52! 
of eggs containing growing tumors. The rise in glutamic acid was accompanied by a 
decrease in glutamine. The same investigators" reported that 2 strains of rats in 
which tumors were produced by methyl cholanthrene or by implantation had in- 
creased levels of free glutamic acid in the blood plasma. 
More recently ROBERTS AND FRANKEL! reported that free glutamine was not 
present in ascites tumor cells of mice. ROBERTS AND TANAKA?® later showed that 
glutamine was absent from both Yoshida ascites tumor cells and the ascitic fluid, 
and that glutamine injected into the ascitic fluid in mice was metabolized rapidly 
by the tumor cells. Injected glutamic acid was not metabolized rapidly, apparently 
because of limited permeability to this amino acid as shown by studies with DL- 
glutamic acid-2-¥C. 
It was evident at the beginning of the studies in humans that a great deal of varia- 
bility was to be expected since there were many conflicting reports in the older 
literature. Reports that have appeared since the beginning of these studies have 
emphasized again the variability. Thus, while we reported a rise in plasma glutamic 
acid and a tendency to lower glutamine in some leukemias?, WAISMAN! failed to 
find such changes, although subsequently KELLEY AND WAISMAN?® using a different 
method did find an elevation of the plasma glutamate level in their leukemia pa- 
tients. NouR-ELDIN AND WILKINSON!® found the fasting plasma amino nitrogen 
concentrations to be within normal limits in patients with different types of leukemia 
before and after treatment, while [yYER! confirmed the rise in plasma glutamic acid 
and also observed decreases in the levels of glutamine and some of the other amino 
acids. SASSENRATH AND GREENBERG!® failed to observe any differences in plasma 
amino acids of rats bearing the Walker carcinoma and could not find any distinct 
pattern of change in the free amino acids of tissues. Later, WU AND BAUER!® reported 
that rats bearing the Walker carcinoma showed no change in the concentration of 
the free amino acids in plasma or tissues when the tumors were small, but as the 
tumors grew larger these investigators noted that the concentrations of most free 
amino acids were increased in plasma and liver and decreased in muscle. They further 
observed that glutamine was the only compound whose concentration was consistently 
decreased in plasma, liver, and muscle. These investigators reported a definite eleva- 
tion of the plasma glutamic acid level in animals bearing both medium and large 
sized tumors. 
BERNARD et al.?° reported highly variable results in their studies of human leuke- 
mias. The blood plasma amino nitrogen was not regularly found to be above normal 
and was, in fact, frequently below the normal level. These studies were complicated 
by the fact that the patients were receiving various drugs. As will be shown in 
subsequent papers in this series, some rather marked changes can be brought about 
by drugs. In agreement with the work of Wu AND BAvER!®, Lutz ef al.?! reported 
that blood amino acid values (determined by the Folin method) of rats with subcuta- 
neous tumors remain relatively unchanged until the terminal stage when a significant 
increase is observed. MCMENAmy et al.?2 in a paper-chromatographic study of 32 
plasma specimens from 23 patients with various types of leukemia, both treated and 
untreated, were unable to find significant differences in plasma glutamic acid and 
glutamine levels. The very small number of samples and the inclusion of treated 
patients in their investigation emphasizes the difficulties in drawing conclusions from 
limited data. 
References p. 447/448 
