894 METABOLISM OF THE CANCER CELL 12 



carried out by Jedeikin and Weinhouse (1955). The ratios of DPN: DPNH in the 

 neoplastic tissues extended over the relatively narrow range of 2.5-4.5. The normal 

 range was 1.2-20. The total content of DPN was generally lower in tumor than 

 in normal tissues although certain normal tissues, i.e., brain and spleen were low 

 in DPN. Some consideration should be given the fact that tumors have a low 

 mitochondrial count. Any significant change in DPN content or the ability of 

 tumor mitochondria to concentrate this factor may exert a considerable influence 

 on the oxidative capacity of these tissues. Weinhouse (1955) suggested the possibility 

 that the permeability of membranes of tumor mitochondria to DPN may be in- 

 creased. 



[f) Fatty acid metabolism 



Interesting quantitative differences occur in the lipid metabolism in tumors 

 (Greenstein, 1954; Weinhouse, 1955). Tumor cells have the capacity to oxidize 

 fatty acids, usually at a reduced rate when compared with normal cells. Most 

 of the investigations in this area have been carried out in normal or cancerous 

 livers and our knowledge of lipid metabolism has been largely obtained from 

 these organs. Compared to normal liver, hepatoma has a greatly reduced capacity 

 to produce acetoacetate from fatty acids (Weinhouse et al. 1953), however, the 

 capacity to oxidize acetoacetate is enhanced. The observed rates of lipid synthesis 

 in some tissues are too slow to account for the fat present, indicating that the 

 tumor has to obtain at least a portion of its lipid from the host (Medes et al., 1953; 

 Wenner and W^einhouse, 1953). Olson (1951), Zamecnik etal. (1951), and Medes 

 et al. (1953) have reported that hepatomas and also other tumors incorporate the 

 carbon of radioactive acetate and glucose into fatty acids. As mentioned, the 

 findings would indicate that the process is too slow to supply the lipid needs of 

 rapidly growing tissues, and that the tumor may have to obtain its lipids preformed 

 from the host. 



A rate differential in the utilization of acetate by tumors has been established 

 by Busch and Potter (1952; 1952a; 1953; Busch 1953, Bush and Baltrush 1954). 

 The utilization of acetate, which occurs readily in the majority of normal tissues, 

 is markedly diminished in several tumors which were tested. Acetate- i-^'*C was 

 injected intravenously into normal rats and into rats bearing the Flexner-Jobling 

 carcinoma, Jensen carcinoma, or W'alker 256 carcinoma: the half-time for disap- 

 pearance of the radiolabeled acetate in most non-tumor tissues was from 6-15 sec, 

 while the half-time in liver was 48 sec, but 4^/2 rnin. for tumors (Busch and 

 Baltrush, 1954). This inability to utilize acetate readily constitutes an important 

 metabolic difference between neoplastic and normal tissues. 



Chapman et al. (1954) studied incorporation of the labeled carbon of octanoate- 

 i-^'^C, octanoate-7-''*C and butyrate-i-^'^C into acetate, and COj by liver slices 

 from normal and tumor-bearing mice, and cell suspensions of motise hepatoma. 

 These investigators concluded that the distribution of carbon^'* in the two positions 

 of acetoacetate, as represented by the C*0 : C*OOH ratio was compatible with the 

 concept of a normal p-oxidation-cleavage-condensation in the tumor. They also 

 studied the incorporation of labeled carbon from acetate- i-^'^C, acetate-2-''*C, 

 propionate- 1 -^"^C, octanoate-i-'^^C, pyruvate-2-''*C and uniformly labeled glucose 



