330 E. ROBERTS AND D. G. SIMONSEN 
integrity of many cell properties, one of which is the maintenance of characteristic 
concentrations of easily extractable ninhydrin-reactive constituents. The increases 
found in amino acid concentrations in the above experiments on the administration 
of hormones to castrated animals are probably not correlated directly with the pro- 
cess of regrowth of the atrophied tissue, but rather reflect the restoration of a meta- 
bolic balance normal for the tissues involved which is necessary for the maintenance 
of normal size and function of these tissues. There is at present no evidence that 
the rate-limiting reactions or processes through which the sex hormones exercise 
their control are directly related to any aspects of amino acid metabolism. 
Free anuno acids of tumor cells and host tissues during progressive growth 
of tumors 
During progressive tumor growth there may be widespread alterations in the metab- 
olism of the tumor-bearing host. Changes may occur in enzyme activities and 
even structure of the tissues, and in nutrition, hormonal balance, and the compo- 
sition of the blood. Particularly great disturbances would be expected to take place 
in the metabolism of the host when the dietary and endogenous sources of nitrogen 
and energy become sufficiently limiting so that they are inadequate to supply both 
the needs of the tumor for growth and the host for maintenance and the available 
building blocks and energy are pre-empted by the neoplasm for its own growth at 
the expense of the normal tissues®!; 52. It was anticipated that some changes might 
be observed in the patterns of easily extractable ninhydrin-reactive constituents in 
the tissues of the tumor-bearing animals during progressive growth of various 
tumors. Studies were made of extracts of liver, kidney, muscle, and brain as well 
as of tumor cells at various times after implantation of ascites tumors into mice and 
rats and during the growth of a solid tumor in rats®?. 
Results obtained in the case of rats bearing the Murphy ascites lymphosarcoma 
are shown in Figs. 239-278. 12 male Sprague-Dawley rats, 45-50 days old, received 
intraperitoneal transplants consisting of 1.7 x 107 tumor cells. Tumor-bearing 
animals were sacrificed at 6h and at I, 2, 3, 4, 5 and 8 days after transplantation, 
at which time the experiment was terminated. Suitable controls were obtained at all 
times. Small amounts of glutamine were detectable in the tumor cells at 48 h (Fig. 
239) after transplantation of the tumor, possibly because of the presence of a small 
number of leucocytes at this time, but this amino acid was not detectable at sub- 
sequent time intervals. During the progressive growth of the tumor there was a 
decrease in the content of glutamic and aspartic acids and glutathione with little or 
no change in the other observable constituents in the tumor cells (Figs. 241, 243, 
245). The pattern of amino acids in the fluid was essentially unchanged during 
the 8 days of observation (Figs. 240, 242, 244, 246). The amino acid patterns of the 
liver during tumor growth were remarkably constant throughout the first 7 days 
of observation (Figs. 247-253), with the exception of the taurine level, which varied 
from one sample to another. In the liver of a terminal animal (Fig. 254) there was 
an increase in contents of ethanolamine phosphate and glutamic acid and a decrease 
in glutamine by comparison with the controls. The only change found in the kidney 
during the course of the experiment (Figs. 255-262) was a decrease in free glutamine 
level at 8 days (Fig. 262). The amino acid patterns in samples of leg muscle of the 
References p. 348/349 
