CARCINOGENESIS 



phenomenon was formerly referred to as adaptive enzyme for- 

 mation but is now known as induced enzyme formation (14). 



Only meager evidence exists for the occurrence of induced 

 enzyme formation in higher organisms. For example, Knox 

 (35) has found that the tryptophan peroxidase activity of 

 mammalian liver increases many-fold in response to injections of 

 large amounts of tryptophan. For a variety of reasons he con- 

 siders this effect due to an increase in the actual quantity of this 

 enzyme. It might be anticipated that the loss of any given 

 enzyme at a particular stage of differentiation or carcinogenesis 

 would lead to the accumulation of the substrate for that enzyme. 

 By the mechanisms of enzyme induction, such an accumulation 

 could then facilitate the increase of enzymes for alternative 

 pathways. 



This schema may give some clues concerning the late 

 manifestations of certain inherited defects. The explanation 

 for some of these imperfections appears intelligible if we con- 

 sider that the responsible defective function is one of the last 

 induced systems to unfold in the developmental process. 



The next stage (cell D) illustrates several interesting changes; 

 the activity of the last special function, labeled H, has reached 

 significant proportions, while the reactions of function S have 

 decreased to an extent where they no longer influence the 

 metabolic pattern of the cell, as shown by the absence of arrows. 

 This cell is a functional one, and the mechanism for reduplica- 

 tion, although still present, is no longer effectively competing 

 for cell food, as indicated by the absence of an arrow from the 

 precursors to the small square. At this stage the cell may still 

 retrace its steps during the process of reduplication or it may 

 continue on its path to final irreversible maturation and death. 

 The path to the irreversible stage is shown by an arrow leading 

 to cell E. This cell has lost its potentiality to reduplicate (note 

 the absence of the square), and all the precursors are funneled 

 into the special functions of the cell. Any mature cell which is 

 no longer capable of multiplication is representative of this 

 stage. Thus, the course of events leading to differentiation is 



685 



