VI SUMMARY 917 



ences in the concentration of enzymes or cofactors, (cl) the relation of hpid oxida- 

 tion to the overall metabolic pattern. Weinhouse and others have observed that 

 many tumors are not self suflicient in the biosynthesis of fatty acids. A further 

 elucidation of this respiratory behavior of the malignant cell will contribute 

 greatly to our knowledge of the origin and growth of these abnormal cells. 



An important contribution to this problem has been made by Busch and 

 associates. Tumors appear to have a lowered capacity to utilize acetate. Labeled 

 acetate is quickly incorporated into the succinate pool in normal tissues, while in 

 carcinoma this conversion is delayed to a considerable extent. Also, tumors do 

 not convert added pyruvate into amino acids as rapidly as most normal tissues. 

 Kit has shown that tumors of lymphatic origin have an unusual capacity to synthe- 

 size glycine and serine and a very limited capacity for the production of aspartic 

 and glutamic acids. Since many quantitative variations occur in various normal 

 cells we cannot say whether the metabolic pattern of a tumor is concerned with 

 the malignant nature of the cell or is quite incidental to this process. The need for 

 further studies in this area which would include a wide spectrum of tumors in 

 several species and more control tissues is obvious. 



Several investigators have found that following administration of labeled plas- 

 ma proteins, the specific activity of proteins in cancerous tissues is higher than 

 in proteins of the normal tissues. This apparent extensive utilization of plasma 

 proteins by malignant tissues would appear highly significant. Several quantita- 

 tive differences in the incorporation of precursors into the nucleic acids of tumors 

 and normal tissues have been reported. These differences in the biosynthesis of 

 nucleic acids in normal and cancerous cells are largely responsible for the action 

 of many of the antimetabolites that have been applied in the chemotherapy of 

 cancer. The establishment of greater quantitative differences or of some unique 

 qualitative differences would provide a basis for a greater success in this area. As 

 the various intermediates are established for the difTerent pathways of nucleic 

 acid formation we may find that such differences do exist. LePage and coworkers 

 have observed that azaserine reacts with constituents of the Ehrlich ascites 

 tumor cell to inhibit purine biosynthesis. An intermediate, glycineamideribotide 

 accumulates, indicating that these tumor cells are inhibited at a point where 

 formylation of this compound occurs. In liver systems, azaserine blocks this reac- 

 tion sequence at a different stage. The significance of this and related studies 

 in the eventual control of the metabolic functions of malignant cells cannot be 

 overemphasized . 



Whether or not the metabolism has any direct relationship to malignant be- 

 havior as mentioned above has not been established. Many different metabolic 

 patterns exist according to the specific tissues or cells involved and tumors may 

 not differ in this respect. Accordingly, we should attempt to explain malignant 

 behavior, or control of the metabolism of tumors at another level. Factors of 

 either intracellular or extracellular origin may control the mobilization of nucleo- 

 proteins and associated processes of cellular reduplication. The nature of these 

 regulatory growth factors is as yet unknown. This regulatory activity may reside 

 within the complex deoxyribonucleoproteins, in simpler structures, or in a com- 

 bination of both. Thus, we may theorize that malignant cells, because of altera- 



Literature p. [jig 



