240 A SYMPOSIUM ON RESPIRATORY ENZYMES 



time for the exceptional results of Orr and Stickland with normal 

 hvers, it can very definitely be stated on the basis of our results 

 and those of Nakatani et ah, that there is a one or more fold increase 

 in the anaerobic glycolytic metabolism (and likewise glucolytic, for 

 those interested in this distinction) of liver tissue in the pre-cancerous 

 stage of butter yellow treatment. That this increase, unless due to 

 a rather inconceivable difference in rat strains, "must have been due 

 to chance," as proposed by Orr and Stickland (13, p. 486), is out 

 of the question, and we prefer the alternate view that the very 

 unusual magnitude and spread of normal liver values obtained by 

 Orr and Stickland have served to confuse rather than to clarify 

 the results they observed with the pre-cancerous livers. A second 

 and regular point of difference in the pre-cancerous livers observed 

 by us was that the initial rate of glycolysis was better maintained 

 over a period of several hours, whereas in the normal livers the 

 Q^^A values dropped to zero or a few tenths in the course of an 

 hour or two, and this relative effect was even more striking when 

 the Q values were based on chemically measured lactic acid rather 

 than on manometric acid production. It is conceivable, in the absence 

 of information to the contrary, that the Orr and Stickland determina- 

 tions on normal liver do not refer to measurements over sustained 

 periods of time (hours), and that in some way the high normal 

 values reported by them involve incidental aspects of initial or 

 preparatory phases of technique, in some measure connected, to be 

 sure, with the glycogen content of livers, as they demonstrated; I 

 hesitate to suggest explicitly the trite explanation of extensive damage, 

 but evidently some factor is operating to give them profoundly 

 atypical (this is not to say incorrect) values for normal liver that 

 certainly make comparisons with other kinds of liver material difficult. 

 Regardless of the foregoing discrepancy of result in regard to 

 pre-cancerous livers, all investigators agree that lactic acid formation 

 from glucose by malignant tumors induced by butter yellow is 

 strikingly different from that of normal liver and definitely or con- 

 siderably increased over any form of pre-cancerous liver, and that 

 the same is true in less marked degree with respect to aerobic lactic 

 acid formation. In general, the anaerobic and aerobic lactic acid 

 productions by these hepatomas are, on an absolute basis, inter- 

 mediate between those of most rat, human, and chicken malignant 

 tumors, on the one hand, studied by Warburg and many others 

 afterward, and, on the other hand, those of certain mouse tumors 

 studied originally by Murphy and Hawkins, and by Crabtree and 



