EFFECTS ON NEOPLASTIC GROWTH 261 



anaerobic glycolysis (Table 1-11), aerobic glycolysis (Table 1-16), glucose 

 utilization (Table 1-22), levels of ATP and creatine-P (Table 1-15), active 

 transport processes (Table 1-31), and others, in which comparisons with 

 normal tissues may be made. The relatively high glycolytic activity raises 

 the possibility that tumor tissue is particularly sensitive to iodoacetate, 

 as is the retina, but by itself does not make this necessarily so. 



Comparison of Metabolic Responses in Tumors and Normal Tissues 



A few investigators have compared inhibitions in tumors and nontumor 

 tissues and, although the interpretation of the results is difficult, it may 

 be of interest to summarize this work. Glycolysis and glucose utilization in 

 tumors are generally depressed more than in normal tissues: Jensen rat 

 sarcoma and rat testis (Krebs, 1931), mouse sarcoma and muscle (Gerard, 

 1931), rat sarcoma and chick embryo connective tissue (Krontowski et ah, 

 1932 a,b), mouse Sarcoma 180 and muscle (Scharles et al., 1935), and Gard- 

 ner mouse lymphosarcoma and lymphatic cells (Villavicencio and Barron, 

 1957). For example, glucose utilization by rat sarcoma is inhibited 70% by 

 0.036 xnM bromoacetate, whereas only 5% inhibition is seen in fibroblasts. 

 Glycolysis in extracts of mouse sarcoma is inhibited 61% by 1 ml/ iodo- 

 acetate with fructose- 1,6-diP as the substrate, whereas only 16% inhibition 

 is seen in comparable muscle extracts. Aerobic glycolysis in mouse lympho- 

 sarcoma is inhibited 85% by 0.01 mM iodoacetate, but only 63% in lym- 

 phatic cells. Similar differences have been noted in phosphate uptake and 

 esterification of phosphate (Scharles et al., 1935; Clowes and Keltch, 1952). 

 In some instances the relative sensitivity may depend on the iodoacetate 

 concentration (Young and Taylor, 1953). The validity of such comparisons 

 is doubtful, however, inasmuch as one should ideally use tumors and homol- 

 ogous tissues (i.e., the same tissue in a normal and in a neoplastic state). 

 Another problem arises when extracts are used, since the metabolic patterns 

 of glucose utilization are quite different in extracts of tumors and normal 

 tissues, due mainly to the discrepancy between the ATPase activities. Cer- 

 tainly inspection of the tables previously presented does not give the im- 

 pression that tumor tissue is particularly sensitive to iodoacetate, nor is 

 there adequate evidence by which to compare the relative susceptibilities 

 of 3-PGDH from tumors and normal tissues. 



There is no doubt that the EM pathway is readily blocked in a variety 

 of tumors by low concentrations of iodoacetate. The following may be 

 mentioned, in addition to those given above: mouse carcinoma (Harrison 

 and Mellanby, 1931), Jensen rat sarcoma (Crabtree and Cramer, 1933 a), 

 Kato spindle cell sarcoma (Tsuzuki, 1936), Yoshida sarcoma (Holzer et al., 

 1958; Schmidt, 1961), Ehrlich ascites carcinoma (Holzer, 1956; Laws and 

 Stickland, 1962), and human mammary fibrosarcoma (van Vals et al., 1956). 

 It may be worthwhile to mention briefly some of the metabohc responses 



