II CARBOHYDRATES AND LIPIDS 893 



general contention that tumors may be characterized by their relatively low 

 activities of cytochrome c, cytochrome oxidase, riboflavin and several other of the 

 oxidative enzymes. Nevertheless, the level of these enzymes in neoplastic tissues 

 is apparently sufficient to maintain the oxidative processes at normal rates. 



Lenta and Riehl (1952) studied the ability of extracts of normal and neoplastic 

 tissues to oxidize reduced DPN. The DPN was reduced enzymatically and the 

 oxidase activity was then determined spectrophotometrically. The oxidative system 

 was analyzed for diaphorase, cytochrome c reductase, and cytochrome oxidase. 

 The considerable reduction in the coenzyme I oxidase system of mouse hepatoma 

 98/15, transplanted sarcoma and adenosarcoma was attributed to the reduction 

 or failure of cytochrome c and cytochrome oxidase. Ascites tumors do not appear 

 to follow the pattern of a lowered cytochrome c and cytochrome oxidase activity 

 as has been noted for other tumors. Chance and Castor (1952) measured the 

 spectra due to cytochrome activity in ascites tumor cells and found a pattern for 

 cytochromes a and a^ similar to that of normal muscle tissue or yeast cells. Cy- 

 tochrome b was low in the ascites cells while cytochrome c was abnormally high. 

 Actually the ratio of cytochrome c to b in the tumor was over four times as 

 great as in normal heart muscle. Subsequently Chance (1953) reported that in 

 suspensions of ascites tumor cells, spectrophotometric observations revealed that 

 cytochrome c, flavoprotein and reduced DPN were present in normal amounts. 

 Schmidt and Schlief (1955) also concluded that the cytochrome c content and cy- 

 tochrome oxidase of ascites tumor are similar to that of liver. The presence of 

 peroxidase in the Walker carcinoma and other growing tissues led Neufeld et al. 

 (1955) to postulate that this enzyme may form part of the respiratory system which 

 would partially replace the conventional cytochrome system. 



The oxidation of pyruvate, citrate, a-keto glutarate, fumarate and malate was 

 increased by factors of from two to ten fold by the addition of DPN to mitochondria 

 obtained from mouse hepatoma 7A77 (Wenner and Weinhouse, 1953). With 

 the addition of DPN, the oxidative response was similar to that obtained with 

 mitochondrial preparations from normal mouse liver. The addition of DPN 

 increased the oxidative and phosphorylative activity of the tumor to the level of 

 normal liver (Kielley, 1952; Wenner and Weinhouse, 1953). This requirement of 

 hepatoma and other tumors for additional DPN cannot be fully explained. The 

 high DPNase activity of tumor mitochondrial preparations was mentioned previ- 

 ously (Williams- Ashman and Kennedy, 1952). Wenner and Weinhouse (1953) also 

 proposed that the mitochondria of tumor do not bind DPN as strongly as normal 

 tissues and that there may be a correspondingly higher level of DPN in the tumor 

 cytoplasm. This would provide a possible explanation for the relatively high 

 glycolytic rate of tumors. Kertesz and Albano (1955) postulated that the high 

 glycolytic activity of tumor may be attributed to some defect between redviced DPN 

 and oxygen. This being the case, the addition of o-diphenol and polyphenoloxidase 

 to reoxidize reduced DPN or TPN should inhibit the high glycolysis and also 

 increase the respiration of tumors. In fact, these investigators did observe that 

 aerobic glycolysis was inhibited and respiration was increased by the addition of 

 diphenol and polyphenoloxidase to the Ehrlich adenocarcinoma system. 



An assay of oxidized and reduced DPN in normal and neoplastic tissues was 



Lileralure p. gig 



