PROBLEMS CONCERNING THE TUMOR VIRUSES 349 



Another advance was made when a strain C58 leukemia was, by means of 

 filtrates, carried through at least 6 serial passages in strain C3H hosts 

 (Gross, 1956). This observation was extended (Gross, 1957a) when a strain 

 AK/n leukemia virus was transmitted through 8 serial passages in C3H mice. 

 The passage virus was procured by using, at each transfer generation, 

 leukemic tissues from the mouse developing the disease earliest. This achieve- 

 ment was important because the virus is now available to other investigators. 

 Gross (1957b) has published a very useful summation of his findings. 



The efforts of other workers to confirm the findings of Gross have met with 

 both failure and success. Stewart (1955a,b) injected extracts and nitrates of 

 AKR leukemias into strain C3H mice, but only 3 of 95 animals developed 

 leukemia. Law et al. (1955) used the techniques described by Gross and, in 

 283 strain C3H mice inoculated with extracts of filtrates from leukemic 

 tissues, observed no increase in the incidence of leukemia beyond that of 

 untreated controls. 



After Gross had become aware of the results of Law and his colleagues he 

 (Gross, 1955a) re-examined the protocols of his experiments and found a 

 striking difference between the incidences of induced leukemia in substrains 

 of C3H mice he had procured from the National Cancer Institute (NCI 

 substrain) and from the Bittner substrain; 320 of the Bittner substrain 

 showed an incidence of 28 %, and 162 of the NCI substrain showed an 

 incidence of only 4 %. This explanation was accepted as the reason for the 

 different findings reported by Stewart and Law, who used NCI mice and those 

 of Gross. Supporting evidence became available when Woolley and Small 

 (1956, 1957) confirmed substrain differences in susceptibility to the virus and 

 also confirmed Gross by using the Gross subline of Bittner mice. Hays et al. 

 (1957) have confirmed the results of Gross by using the Gross subline of 

 strain C3H and also strain C57BR/cd mice. Law (1957) investigated the origins 

 of different C3H substrains and found that the NCI strain has shown a low 

 incidence of leukemia since its separation from the parent strain in 1930; the 

 highest reported incidence was 10 % (Dunn, 1954). The Bittner substrain 

 originated in 1931 and Gross procured his subline from Bittner in 1944. 

 Differences between the various substrains of strain C3H have been recognized 

 and ascribed to genetic differences (Law, 1957). 



Law (1957) procured C3H mice from Bittner and observed the occurrence 

 of spontaneous leukemia in them. Gross has repeatedly stated that his 

 subline of Bittner's mice rarely develop leukemia and that the incidence is 

 less than 0.5 %. Woolley and Small (1956) found 2 mice with leukemia in 

 144 untreated C3H mice of the Gross subline and Dulaney et al. (1957) found 

 8 cases in 83 untreated C3H mice which were descendants of litters procured 

 from Gross. In this report Dulaney also included results attending the inocula- 

 tion of AKR and AK/n leukemic extracts into C3H mice of the NCI and 



