102 F. B. BANG 



and since intranuclear inclusions occur in these tumor cells (Lucke, 1939), 

 it is generally accepted that this tumor is caused by a filterable agent. 

 Since investigation of the agent is still preliminary, this discussion will be 

 limited to the cytological changes which differentiate the tumor cells from 

 normal. 



The recent much-needed tissue culture studies of Duryee (1956) have 

 brought us much closer to realizing a method by which a known number of 

 virus particles may be placed on a known number of cells so that the morpho- 

 logical events involved in a one-step growth curve may be followed. The 

 changes, which he has labeled as precancerous, may then eventually be quite 

 precisely determined. 



Under less exact conditions, Duryee (1956) has studied the following 

 changes produced by this virus in living cells: (1) Large irregular nucleoli, 

 which often showed pulsations. (2) Large cytoplasmic inclusions, which were 

 thought to originate in the nucleus, and were seen passively to extrude 

 through the nuclear membrane. (3) Giant cells with 3 to 55 nuclei per cell. 

 In addition to these direct observations, it was determined by means of a 

 microdissector that the intranuclear inclusions were semisolid, gelatinous 

 masses (Fig. 18). 



An electron microscope study of these tumors by Fawcett (1956) has 

 revealed numerous "virus particles" throughout these cells in about one-third 

 of the tumors examined. These are hollow spheres (90-100 m/x) with a thick 

 capsule and a dense inner body (35-40 nut). These particles were found in 

 the cytoplasm, occasionally in the nucleus, and in the microvilli, where they 

 were presumably being extruded into the extracellular spaces (Fig. 19). 



The intranuclear inclusion bodies which are described above were found 

 to be largely made up of hollow spherical vesicles with a thin limiting mem- 

 brane. These are thought to be "immature virus particles." A few of these 

 contain a dense inner body like the "mature" cytoplasmic particles. Bundles 

 of dense filaments and vacuoles, which were also found in the infected cells, 

 were not explained. A sequence of development of the virus is suggested, 

 but, again, is completely dependent upon hypothetical order of events. 



In summarizing the distribution of virus particles in the different virus 

 tumors we have included data on the Shope fibroma, even though it is re- 

 viewed in another section. It is evident that the tumor viruses, like other 

 viruses, are found throughout the cell. Moreover, there is nothing distinctive 

 about the type of cell pathology produced by them. This lends credence to 

 the idea that these tumor cells in which virus is found and changes are 

 produced are the cells which are out of balance with their parasitic virus. 

 Thus, the balanced state, which indeed may be one analogous to that of the 

 lysogenic bacteria, has not as yet been technically distinguishable from the 

 normal cell. 



