54
Ν. G. PON
that glucose goes all the way to the level of triose phosphate before
forming some of the deoxyribose since glucose-l-C
14
yields deoxyribose
labeled in the 5-position. Disturbing is the fact that, even now, the
mechanism by which deoxyribose is synthesized remains obscure. Although Racker (347) found in Escherichia coli an enzyme system that
will catalyze the condensation of acetaldehyde with glyceraldehyde-3phosphate to form deoxyribose-5-phosphate, the reaction seems to be
more in favor of the cleavage of deoxyribose phosphate than the formation. In studies with animal cells and bacteria there is a body of data
to indicate that ribose is directly converted to deoxyribose while maintaining the glycosidic linkage intact in the nucleoside or nucleotide. A
full account of this story is given by Beck (348).
The anaerobic utilization of ribose-5-phosphate by neoplastic tissues
is relatively high when compared with normal tissues (349). Mouse
ascites tumor cells do not degrade ribose after incubating for 4 hours,
on the other hand (350). In the presence of radioactive bicarbonate,
carboxyl-labeled lactate is formed, suggesting that an active phosphoribulosekinase and carboxydismutase are present in these tissues (349).
We (N. G. Pon and Κ. K. Lonberg-Holm, unpublished results) have
tested this hypothesis and found that, at least in cell-free homogenates
of the Ehrlich ascites mouse tumor, no carboxydismutase is present. The
labeling pattern can be explained by invoking the dicarboxylic acid
shuttle. It might be surprising that ribose-5-phosphate is utilized at all
owing generally to the nonpermeable nature of phosphorylated compounds, but Wu (351) demonstrated that certain enzymes preferentially
leak from these tumor cells. Thus, he found that all glycolytic and pentose phosphate cycle enzymes (transketolase and transaldolase) were
released into the suspending medium. Glyceraldehyde-3-phosphate dehydrogenase was rapidly inactivated, however, so that the metabolic
pattern, after the addition of ribose-5-phosphate in vitro to the medium,
was different from that of a total cell homogenate.
If cancer cells are to be considered as arising from host cells, then
the problem of when a change in the metabolism of the developing
tumor occurs should be faced. Experiments with tumors induced by
9,10-dimethyl-l,2-benzanthracene in hamsters' cheek pouches were conducted (352). During the development of the tumor, five different
periods were recognized: I, no change, ca. 1st week; II, inflammation,
2nd and 3rd weeks; III, hyperplasia, after 3rd week; IV, preneoplastic
hyperplasia and appearance of papillomas, ca. 7th week; and V, appearance of malignant tumor. Hexokinase, G-6-P DH, and 6-PG DH activities
were assayed and were found to display different behaviors during the
development of the neoplastic stage. Hexokinase activity is low in period
Ν. G. PON
that glucose goes all the way to the level of triose phosphate before
forming some of the deoxyribose since glucose-l-C
14
yields deoxyribose
labeled in the 5-position. Disturbing is the fact that, even now, the
mechanism by which deoxyribose is synthesized remains obscure. Although Racker (347) found in Escherichia coli an enzyme system that
will catalyze the condensation of acetaldehyde with glyceraldehyde-3phosphate to form deoxyribose-5-phosphate, the reaction seems to be
more in favor of the cleavage of deoxyribose phosphate than the formation. In studies with animal cells and bacteria there is a body of data
to indicate that ribose is directly converted to deoxyribose while maintaining the glycosidic linkage intact in the nucleoside or nucleotide. A
full account of this story is given by Beck (348).
The anaerobic utilization of ribose-5-phosphate by neoplastic tissues
is relatively high when compared with normal tissues (349). Mouse
ascites tumor cells do not degrade ribose after incubating for 4 hours,
on the other hand (350). In the presence of radioactive bicarbonate,
carboxyl-labeled lactate is formed, suggesting that an active phosphoribulosekinase and carboxydismutase are present in these tissues (349).
We (N. G. Pon and Κ. K. Lonberg-Holm, unpublished results) have
tested this hypothesis and found that, at least in cell-free homogenates
of the Ehrlich ascites mouse tumor, no carboxydismutase is present. The
labeling pattern can be explained by invoking the dicarboxylic acid
shuttle. It might be surprising that ribose-5-phosphate is utilized at all
owing generally to the nonpermeable nature of phosphorylated compounds, but Wu (351) demonstrated that certain enzymes preferentially
leak from these tumor cells. Thus, he found that all glycolytic and pentose phosphate cycle enzymes (transketolase and transaldolase) were
released into the suspending medium. Glyceraldehyde-3-phosphate dehydrogenase was rapidly inactivated, however, so that the metabolic
pattern, after the addition of ribose-5-phosphate in vitro to the medium,
was different from that of a total cell homogenate.
If cancer cells are to be considered as arising from host cells, then
the problem of when a change in the metabolism of the developing
tumor occurs should be faced. Experiments with tumors induced by
9,10-dimethyl-l,2-benzanthracene in hamsters' cheek pouches were conducted (352). During the development of the tumor, five different
periods were recognized: I, no change, ca. 1st week; II, inflammation,
2nd and 3rd weeks; III, hyperplasia, after 3rd week; IV, preneoplastic
hyperplasia and appearance of papillomas, ca. 7th week; and V, appearance of malignant tumor. Hexokinase, G-6-P DH, and 6-PG DH activities
were assayed and were found to display different behaviors during the
development of the neoplastic stage. Hexokinase activity is low in period