178 F. Dickens, G. E. Clock and P. McLean 



be explained by decreased DPN pyrophosphorylase activity 

 (Clock and McLean, 1958, unpublished). DPNase or TPNase 

 activity might be increased, but this requires investigating. 

 It is of interest that the activities of two of the enzymes con- 

 cerned with the reoxidation of TPNH are altered by thyroxine. 

 TPNH cytochrome c reductase activity is approximately 

 doubled in the liver of hyperthyroid rats (Phillips and Lang- 

 don, 1956) whereas thyroxine inhibits the in vitro oxidation of 

 TPNH by transhydrogenase (Ball and Cooper, 1957). Inhibi- 

 tion of transhydrogenase activity, if it occurs in vivo, might 

 perhaps be expected to result in a lower yield of high-energy 

 phosphate. 



The total DPN content of DAB hepatomata is approxi- 

 mately half that of normal Uver. The DPN+/DPNH quotient, 

 however, is unaltered. The total DPN contents of a large 

 range of tumours are very similar to those quoted in Table V 

 (Jedeikin and Weinhouse, 1955; Clock and McLean, 1957) 

 and in all cases the DPN+/DPNH quotient is not significantly 

 different from that of normal tissues (Clock and McLean, 

 1955a). The unaltered DPN+/DPNH quotient is somewhat 

 surprising in view of the high lactic acid concentrations in 

 many tumours which would be expected to be reflected in 

 this quotient. Of more interest is the finding that the total 

 TPN (chiefly TPNH) content of all the tumours investigated 

 is extremely low (Clock and McLean, 1957). As shown in 

 Table V, there is a gradual fall in the total TPN content of 

 rat liver undergoing carcinogenesis with DAB, the TPN 

 content of the liver adjacent to the tumours being less than 

 half that of normal liver. 



The relatively low DPN content of tumours cannot be 

 attributed to increased DPNase activity (Quastel and Zatman, 

 1953) and is presumably due to decreased DPN pyrophos- 

 phorylase activity, since Branster and Morton (1956) and 

 Morton (1958) have found a marked reduction in the activity 

 of this enzyme in certain tumours. The results in Table V 

 suggest, in addition, that synthesis of TPN from DPN is also 

 severely depressed in DAB tumours. 



