PROBLEMS CONCERNING THE TUMOR VIRUSES 351 



He recorded a leukemia incidence of almost 50 % in first generation progeny 

 of infected C3H parents but a "rather low" incidence in two subsequent 

 generations. He concluded that his attempt to obtain a high-leukemia line of 

 strain C3H was unsuccessful and, of more interest, modified his original 

 theory of an ever present virus in descendants of infected mice to include the 

 possibility that the virus "may either completely disappear, or it may 

 become so submerged and masked, as to lose, with only occasional exceptions, 

 its ability to become activated spontaneously." It is strange that others who 

 have followed Gross' procedures have not pursued the important implication 

 in his first reports of generation-to-generation transfer of the virus. Dulaney 

 et al. (1957), without including data, stated they had not confirmed Gross' 

 observation. Perhaps, as with the virus of mouse mammary cancer, only 

 certain inbred strains will accept and transmit the leukemia virus; it is 

 essential to ascertain whether such strains are available. The transformation of 

 a low -leukemia strain to a high-leukemia strain would help establish the 

 viral etiology of the disease because virus-free mice of the same inbred strain 

 would be available for comparison. If the disease is "egg-borne," as claimed 

 by Gross, then it may be impossible to free infected strains of the virus, and 

 this should encourage the search for other strains capable of transmitting the 

 virus through successive generations. It is difficult to understand why studies 

 with this tumor virus have been limited to only a few inbred strains as test 

 animals when so many are available, and why the techniques for trans- 

 plantation of ovaries and fertilized ova have not been used more extensively 

 (Fekete and Otis, 1954) to explore its natural routes of transmission. 



b. Hybrids as Test Animals. First generation hybrids procured from inbred 

 strains may be useful in studies with any virus. Stewart (1955b) obtained 

 hybrids by mating low-leukemia strain C3H females to high-leukemia strain 

 AXE males and inoculated them with filtrates of AKR leukemic tissues. 

 When the hybrids were 9 months old, 22 of 45 inoculated mice had developed 

 leukemia, in contrast to only 2 of 44 untreated controls. Law et al. (1955) 

 inoculated similar hybrids with extracts, centrifugates, or filtrates of leukemic 

 tissues from various sources. They observed, similar to the findings of Stewart, 

 a 4.5 % incidence of leukemia in the inoculated mice before the disease 

 occurred in any of the controls but, at 18 months of age, the incidence in 

 inoculated mice was 18.6 % and in the untreated controls 54 %. Hays et al. 

 (1957) have reported interesting preliminary results with (C3H X AKR)F X 

 hybrids. They prepared nucleic acid preparations of normal and leukemic 

 lymph glands and spleens from AKR mice and injected them into mice of 

 strains C3H, C57BR/cd, and (C3H X AKR)F X hybrids. Preparations from 

 leukemic tissues did not produce leukemia in C3H or C57BR/cd mice, but 

 those from both nonleukemic and leukemic tissues accelerated the occurrence 

 of leukemia in the hybrids. 



