PROBLEMS CONCERNING THE TUMOR VIRUSES 347 



For the object of this discussion, these factors make it difficult to present a 

 review which most readers can easily understand. Perhaps the best approach 

 is to follow the experiments reported by Gross, who supplied recent evidence 

 for the viral etiology of mouse leukemia, and to refer to others when their 

 results are applicable to his findings. It is hoped that this procedure will 

 assist the reader in focusing attention upon separate facets of the problem at 

 different times and avoid the confusion which usually prevails when the work 

 is presented chronologically. 



1. Leukemia 



The first publication by Gross (1950) described experiments in which mice 

 of the inbred strains C3H and C57BL were inoculated subcutaneously with 

 cell suspensions of leukemic tissues from strain AK/n mice 1 bearing a trans- 

 plantable leukemia. The tumor grew in some recipients of both strains, but 

 1-to 7-day-old C3H and 1-day old C57BL mice were far more susceptible 

 than older mice of the same strains and these latter animals displayed an 

 increasing resistance with increasing age. Gross concluded with the statement: 

 "It remains to be seen whether all these mice . . . that did not apparently 

 react to the inoculation of the leukemic-cell suspensions will remain free from 

 leukemia for the balance of their lives." Gross (1952a) supplied the final 

 information concerning strain C3H only. Of 62 mice that had received cell 

 suspensions when 8 to 60 days old, 25, or 40 %, developed leukemia between 

 the ages of 13 and 24 months without any evidence of tumors at the site of the 

 initial inoculation. 



The occurrence of leukemia in these animals is of considerable interest 

 because in most of his later papers Gross emphasized the importance of 

 using newborn mice (less than 16 hours old) for the detection of the virus, 

 although in his earlier work (Gross, 1951b, 1952b) mice up to 8 days of age 

 were susceptible. He used 43, 22, and 7 mice when they were 2-7, 2-6, and 8 

 days old, and 11, 12, and 2, developed leukemia at average ages of 17.6, 17.8, 

 and 25 months, respectively. It is difficult to correlate these findings with 

 his statement a few years later (Gross, 1954a) that: "Newborn mice less than 

 16, or better, less than 12 hours old had to be injected in order to successfully 

 transmit the leukemic agent and cause the development of leukemia in the 

 inoculated animals. When older mice were inoculated, the results were either 

 negative, or considerably delayed and erratic." It is true the results were 



1 The standardized nomenclature for inbred strains of mice and their hybrids, pre- 

 pared by a committee (1952) appointed for this purpose, is used throughout this chapter. 

 The designation AK/n refers to a line, maintained by Gross, of the high-leukemia AKR 

 strain. When authors refer to their mice as the AK strain, the writer used his best 

 judgment in the use of the AKR and AK/n designations. 



First generation hybrids derived from two inbred strains, such as strain C3H and 

 strain AKR, are designated as (C3H X AKR)Fi hybrids. 



