52
Ν. G. PON
Ehrlich ascites tumor, 23% (see Alsenberg, 338). Abraham et al. obtained
a range of 0.28-0.58 in mouse C 954 hepatocarcinoma as the fraction of
the fatty acids derived from glucose via the shunt mechanism
(341).
The liver of the tumor-bearing mouse (as well as of the normal mouse),
on the other hand, converts glucose to fatty acids mainly through the
EMP pathway; i.e., the relative contribution of the pentose phosphate
cycle toward the formation of fatty acids from glucose is nearly zero.
Weber and his associates have studied the fate of glucose-6-phosphate
in hepatoma in four different directions: glycolysis, the direct oxidative
pathway, glycogenesis, and glucose release (342). Indicator enzymes
for each of these four routes were phosphohexose isomerase, G-6-P DH,
phosphoglucomutase, and glucose-6-phosphatase, respectively. Isotopic
studies were also conducted in order to yield a quantitative estimate of
the pathways taken by glucose during its metabolism in normal liver
and hepatomas, the results of which are summarized in Table IX. Clearly
TABLE IX
PERCENTAGE OF GLUCOSE-6-PHOSPHATE METABOLIZED VIA VARIOUS PATHWAYS
IN THE NORMAL RAT LIVER AND THE NEOPLASTIC LIVER (842)
Liver tissues
Glycolysis
Shunt
Glycogenesis
Glucose
formation
Normal liver
25
2
18
55
Morris no. 5123 hepatoma
65
2
1
32
Novikoff hepatoma
88
10
2
0
then, glycolysis is markedly increased in the Morris No. 5123 hepatoma
and in the Novikoff hepatoma whereas the pentose phosphate cycle
activity is enhanced only in the Novikoff hepatoma. Both glycogenesis
and glucose formation are decreased significantly in both hepatomas.
These conclusions are supported, at least in two cases, by the changes in
levels of enzymes concerned with the metabolism of glucose-6-phosphate;
especially those of the hexose monophosphate shunt and of the glucose
production (Table X). Inspection of other types of hepatomas of varying
growth rates showed a definite trend as to the cellularity, the nitrogen
content, and the glucose-6-phosphate dehydrogenase activity
(343).
Thus, the Morris No. 5123 hepatoma, with a slow growth rate (60-90
days), has a lower cellularity, a higher nitrogen content, and a lower
G-6-P DH activity than the Reuber hepatomas, No. 5123 t.c, No. 3924A,
No. 7288 B, and No. 3683, which have intermediate growth rates. The
Novikoff tumor with a 7-day growth rate, has the highest cellularity, the
lowest nitrogen content, and the highest G-6-P DH activity.
Another much-studied tumor is the Ehrlich ascites mouse tumor.
Ν. G. PON
Ehrlich ascites tumor, 23% (see Alsenberg, 338). Abraham et al. obtained
a range of 0.28-0.58 in mouse C 954 hepatocarcinoma as the fraction of
the fatty acids derived from glucose via the shunt mechanism
(341).
The liver of the tumor-bearing mouse (as well as of the normal mouse),
on the other hand, converts glucose to fatty acids mainly through the
EMP pathway; i.e., the relative contribution of the pentose phosphate
cycle toward the formation of fatty acids from glucose is nearly zero.
Weber and his associates have studied the fate of glucose-6-phosphate
in hepatoma in four different directions: glycolysis, the direct oxidative
pathway, glycogenesis, and glucose release (342). Indicator enzymes
for each of these four routes were phosphohexose isomerase, G-6-P DH,
phosphoglucomutase, and glucose-6-phosphatase, respectively. Isotopic
studies were also conducted in order to yield a quantitative estimate of
the pathways taken by glucose during its metabolism in normal liver
and hepatomas, the results of which are summarized in Table IX. Clearly
TABLE IX
PERCENTAGE OF GLUCOSE-6-PHOSPHATE METABOLIZED VIA VARIOUS PATHWAYS
IN THE NORMAL RAT LIVER AND THE NEOPLASTIC LIVER (842)
Liver tissues
Glycolysis
Shunt
Glycogenesis
Glucose
formation
Normal liver
25
2
18
55
Morris no. 5123 hepatoma
65
2
1
32
Novikoff hepatoma
88
10
2
0
then, glycolysis is markedly increased in the Morris No. 5123 hepatoma
and in the Novikoff hepatoma whereas the pentose phosphate cycle
activity is enhanced only in the Novikoff hepatoma. Both glycogenesis
and glucose formation are decreased significantly in both hepatomas.
These conclusions are supported, at least in two cases, by the changes in
levels of enzymes concerned with the metabolism of glucose-6-phosphate;
especially those of the hexose monophosphate shunt and of the glucose
production (Table X). Inspection of other types of hepatomas of varying
growth rates showed a definite trend as to the cellularity, the nitrogen
content, and the glucose-6-phosphate dehydrogenase activity
(343).
Thus, the Morris No. 5123 hepatoma, with a slow growth rate (60-90
days), has a lower cellularity, a higher nitrogen content, and a lower
G-6-P DH activity than the Reuber hepatomas, No. 5123 t.c, No. 3924A,
No. 7288 B, and No. 3683, which have intermediate growth rates. The
Novikoff tumor with a 7-day growth rate, has the highest cellularity, the
lowest nitrogen content, and the highest G-6-P DH activity.
Another much-studied tumor is the Ehrlich ascites mouse tumor.