892 METABOLISM OF THE CANCER CELL 12 



mal and neoplastic tissues are nearly equal (Potter and Liebl, 1945). The acid 

 phosphatase was not altered significantly during the different stages of growth 

 or regression of the Flexner-Jobling carcinoma. The alkaline phosphatase values 

 were considerably elevated in the growing tumors (Foder et al., 1955). 



Williams-Ashman and Kennedy (1952), in studying oxidative phosphorylation, 

 prepared mitochondrial fractions from tumors. Succinate was added as sub- 

 strate and fructose hexokinase as the terminal phosphorus acceptor system. By 

 use of ^^P it was observed that there was considerable incorporation of phos- 

 phorus into the lipids, nucleic acid and residual protein fractions. The dependence 

 of this process upon the substrate as well as inhibition by DPN led these investi- 

 gators to conclude that glycolytic mechanisms could not account for the observed 

 synthesis. They further indicated that tumor cytoplasmic fractions possess the 

 same aerobic mechanisms for the generation of high energy phosphate components 

 as are operative in other mammalian tissues. Lindberg et al., (1953) reported that 

 both respiration and phosphorylation were low in mitochondria prepared from 

 Ehrlich ascites tumor, the rate of phosphorus uptake in micromoles of phosphorus 

 per mg of nitrogen per min. being between 0.05 and 0.3 with various substrates. 

 A value of two was obtained for normal mouse liver and four for rabbit heart. The 

 P/O ratios were also depressed in the tumor mitochondrial preparations. ATPase 

 from tumor mitochondria was capable of destroying the ATP required for the 

 formation of the acyl coenzyme A bond, according to Emmelot and Bos (1955). 



Siekevitz and Potter (1953), and Wenner and Weinhouse (1955) have studied 

 the effects of dinitrophenol and fluoride on oxidation in normal and tumor 

 tissues. The former investigators added both of these factors to several different 

 tumor tissues and all gave somewhat different patterns of oxidative response. 

 Wenner and Weinhouse reported that dinitrophenol stimulated glucose oxidation 

 in neoplastic and normal tissues at low concentrations and inhibited at higher 

 concentrations. Their conclusions are summarized as follows: "The neoplastic 

 cell does not differ in any fundamental respect from non-neoplastic tissues in 

 mechanisms of phosphorylation, and dephosphorylation associated with glucose 

 metabolism". Clowes and Keltch (1952) also observed that by adjustment of 

 chloride concentration, the preponderance of glycolytic over oxidative phos- 

 phorylation in Walker 256 carcinoma was considerably enhanced. Phosphoryla- 

 tion in this tumor appeared to differ from that in normal tissues mostly on a quan- 

 titative rather than on a qualitative basis. 



The effect of diethylstilbestrol and benzoquinone on the interrelationships be- 

 tween respiratory, phosphorylative and mitotic activities in Ehrlich ascites tumor 

 cells was studied by Shacter (1956). Both of these compounds in increasing concen- 

 trations inhibited cellular respiration and altered the acid soluble components. 

 At higher concentrations the permeability of cellular membranes was also affected. 



{e) Electron transport 



Weinhouse (1955) gave an excellent summary of the present status of the elec- 

 tron transport system. Greenstein (1954) has also provided a compilation of the 

 contents and activities of the aerobic enzymes and cofactors that are present in 

 many normal and neoplastic tissues. As has already been mentioned, there is a 



