PKOBLEMS CONCERNING THE TUMOR VIRUSES 317 



the twenty-second passage, there was increasing frequency of "typical 

 hemorrhagic disease" in the inoculated chicks. Hepatic lesions appeared 

 during the twenty-fifth passage and also occurred with increased frequency in 

 subsequent passages. Tests for correlation between the dose of virus and 

 incidence of hemorrhagic disease and hepatic lesions showed that both were 

 associated with the inoculation of larger amounts of virus, but more virus was 

 required to provoke liver lesions than the hemorrhagic disease. Finally, a 

 large dose of the virus used as source material for the brain passages also 

 produced both hemorrhagic disease and liver lesions in 1 -day-old chicks. 

 Thus, the occurrence of liver lesions and hemorrhagic disease was dependent 

 upon the quantity instead of the quality of the virus. 



Experiments of this sort do not refute the idea that tumor viruses are 

 subject to alterations of a genetic nature, but they do serve as a warning 

 signal to those who are prone to interpret a change in the response to a virus 

 as a change in the virus itself without first excluding a quantitative relation- 

 ship between host and virus or a qualitiative change in the host. 



Various substances have been tested for their abilities to alter the response 

 of the host to the Rous sarcoma virus (Harris, 1953). A recent publication by 

 Groupe et at. (1956a) serves to illustrate how treatment of the host can 

 influence its reaction. These investigators found that the administration of 

 hydrocortisone to chicks less than 7 days of age gave different results, 

 depending upon the dose of hydrocortisone and the time of virus administra- 

 tion. When daily large doses of hydrocortisone were started 2 days before 

 inoculation, the tumors appeared later in treated than in untreated control 

 birds; when small doses were used, tumors occurred in experimental and 

 control animals at the same time, but the experimental animals developed 

 larger tumors. Further, the tumors in animals receiving larger amounts of 

 the compound were firm and sharply circumscribed, in contrast to the soft 

 and invasive tumors in the controls. It is of special interest that soon after 

 cortisone treatment was stopped the altered tumors grew rapidly and soon 

 resembled those of the control animals. When daily large doses of hydrocor- 

 tisone were started 2 days after the virus was administered, the tumors were 

 invasive and grew more rapidly than those in the control animals. The timing 

 and dose of the compound exerted a pronounced influence upon the host's 

 reaction to the virus. 



Groupe et al. (1956b) reported the results of daily injections of Xerosin 

 started 2 days before inoculation of 2 to 5-day-old chicks with varying amounts 

 of the Rous virus. Xerosin delayed the occurrence of tumors in the treated 

 chicks but was most effective in chicks that had received small amounts of 

 virus; that is, the effectiveness of Xerosin was determined largely by the 

 amount of virus used to initiate the tumor. Injections of Xerosin also produced 

 firm and circumscribed tumors similar to those appearing after treatment with 



