gi6 METABOLISM OF THE CANCER CELL 12 



In 1 2 cases of clinical cancer the oxygen content of venous blood draining the 

 tumor was higher than that in other parts of the body. This was interpreted as 

 being the result of an increased blood flow through these tumors (Bierman et al., 

 1952). Tumor tissues, as has been shown by Warburg and others usually have a 

 low oxygen tension. Recently Urbach (1956) has demonstrated that tumors have 

 a verv low oxygen tension as compared to that of the immediate adjacent tissues. 

 This decrease of tissue oxygen tension may be due to a combination of diminished 

 capillary flow and an increase in the oxygen consumption of the tumor. 



Two types of transplantable tumors were found in female mice exposed to 

 whole body ionizing irradiation: adrenotrophic and mammatrophic (Furth et al., 

 1956, 1956a). Hyperestrogenization may be the growth stimulant for the latter 

 type. The mammotrophic tumor induces mammary gland hyperplasia and also 

 some somatrophic effects. These investigators attribute both the mammotrophic 

 and somatrophic effects to a single hormone secreted by the tumor. Newman and 

 McCoy (1956) have recently reported that Walker 256 carcinoma cells, in vitro 

 have a dual requirement for both aspargine and glutamine and do not require the 

 corresponding amino acids. This unusual requirement does not occur in any 

 known living system. 



VI. SUMMARY 



There is no conclusive evidence, as yet, that malignant cells may differ qualitative- 

 ly from normal cells either in their metabolic or compositional patterns. The 

 same precursors, enzymes and metabolic pathways are present and operative in 

 normal as well as in cancerous tissues. Many quantitative differences in the con- 

 centration of the enzymes or the intermediary metabolites have been reported for 

 individual tumors. In some respects, tumors may be characterized or classified 

 as a group by the concentration or activities of the metabolic constituents. A 

 good example of this is the generally lowered concentration of the B vitamins and 

 many of the oxidative enzymes in neoplastic tissues. However, no consistent pat- 

 tern has been found that would distinguish malignant cells from the many normal 

 cellular types. Since malignant cells differ from normal cells in other aspects such 

 as morphology, rate of division, lack of response to inherent growth regulatory 

 mechanisms, metastatic tendencies, etc, we must attribute these differences either 

 to an altered intermediary metabolism or to other levels of cellular activity. The 

 possibility does exist that the same metabolites and pathways present in normal 

 tissues may undergo quantitative rearrangements that would give rise to a malig- 

 nant prototype. We have no definite proof that this is the case. 



All of the enzymes and the various intermediates involved in the breakdown of 

 glucose and the operation of the citric acid cycle are apparently present in malig- 

 nant cells. However, these cells are generally characterized by high aerobic and 

 anaerobic glycolytic rates. This metabolic feature has been attributed to one or a 

 combination of these factors; (a) disturbances in the electron transport system, 

 (b) differences in membrane permeability between normal and cancerous cells 

 limiting the exchange and availability of essential metabolites, (c) relative differ- 



