HAROLD P. RUSCH 



that the carcinogenic activity of the compounds tested is cor- 

 related with the amount or rate of binding (44,45). Collabora- 

 tive experiments by Potter, Price, Miller, and Miller (50) have 

 demonstrated pronounced progressive decreases in certain cyto- 

 plasmic enzymes during carcinogenesis in the rat liver. 



Third, if nucleic acids or nucleoproteins as pure chemical 

 entities or in a form carried by viruses can be passed from one 

 strain of cells to another and thereby induce or transduce herit- 

 able alterations in the metabolic pattern in bacteria, one must 

 inquire whether similar phenomena occur in some types of car- 

 cinogenesis. At present there are only the cases in which viruses 

 have been shown to convert normal cells to cancer cells (10, 

 53,54,61), and it is not clear whether the process is analogous to 

 transduction or lysogeny or whether the introduction of the 

 virus leads to a cytoplasmic deletion by competitive interaction. 

 It appears probable that the viruses act at the cytoplasmic 

 level and that their action is not strictly analogous to the DNA 

 transformations, which evidently act at the nuclear level. 



It is of interest to recall at this time that a phenomenon 

 similar to transduction or lysogeny was foreshadowed and il- 

 lustrated by the pioneer work of Peyton Rous and his associates 

 (55) when they demonstrated that a cell-free extract of an os- 

 teochondrosarcoma could "transduce" connective tissues in 

 voluntary muscle into osteochondrosarcomas. The implication 

 of this finding was not lost to them, since in 1912 they stated 

 (55), "It is very remarkable that such an agent should bring 

 about a differentiation ordinarily foreign to the tissue." 



The solution of carcinogenesis would be complicated enough 

 if a thorough understanding of the mechanisms of heritable 

 cellular changes were the only aspect of the problem requiring 

 clarification. It is now recognized that the formation and 

 growth of some tumors are prolonged processes, in some types 

 involving three or more separate periods : ( 7) the stage in which 

 a heritable cellular change occurs (called the period of initiation), 

 (2) the period called promotion, in which the altered cells pro- 

 liferate and become an autonomous cluster, and (3) the period 



680 



