PROBLEMS CONCERNING THE TUMOR VIRUSES 339 



histologically similar to those procured with, the virus but arose in mice at a 

 later average age than did the virus-induced tumors. Hybrids were obtained 

 from mice of various inbred strains which were presumably free of the virus, 

 those derived from strains susceptible to the virus showed the highest 

 incidences of tumors (Andervont and Dunn, 1948a). In the discussion of these 

 findings it was suggested that the virus could act as an accelerator in the 

 production of tumors because, in the agent-free hybrids, tumors arose in 

 mice of certain genetic derivations and only after they had experienced 

 considerable hormonal stimulation. 



Heston el al. (1950) reported a relatively high incidence of breast tumors in 

 members of a substrain of strain C3H mice which were free of the agent. This 

 substrain was procured by removing a litter by cesarean section from a 

 high-tumor strain C3H female and foster-nursing them upon a low-tumor 

 strain C57BL female. The first five generations of the substrain were bred 

 intensively and showed a mammary tumor incidence of 38 % at a mean age 

 of 20 months. Further, mice with tumors were not members of certain 

 families which would be expected if the virus had gained access to a few 

 females. It was concluded that the tumors arose in agent-free mice because of 

 their genetic composition and intensive breeding. 



Additional evidence of breast tumor production in virus-free mice was 

 disclosed when they were used as experimental animals in investigations in- 

 volving the occurrence of breast tumors in mice subjected to skin painting 

 with the carcinogenic hydrocarbon methylcholanthrene. Mider and Morton 

 (1939) applied the carcinogen to the skin of virus-carrying strain DBA 

 mice and found that the painted mice developed mammary tumors much 

 earlier than did control animals. Later, Andervont and Dunn (1950) and 

 Bittner and Kirschbaum (1950) used the same technique for producing 

 breast tumors in virus-free DBA mice and did not find the virus in the 

 induced tumors. Dmochowski and Orr (1949) obtained similar results, but 

 with mice of strains IF and C57BL, which were relatively resistant to the 

 virus. 



Despite evidence that the virus was not involved in the occurrence of these 

 mammary tumors, Dmochowski (1953b) questioned this interpretation after 

 an extensive investigation in which hybrids derived from virus-free C57BL 

 females and virus-containing RIII males were used. The progeny of some of 

 the female hybrids developed mammary tumors and, of 23 such tumors 

 assayed for the virus, 17 were found to contain it. Dmochowski discussed his 

 findings in relation to those of others and suggested: "The conclusion that 

 tumors in old hybrids do not harbour the agent and are the result of a 

 combined action of hormonal and genetic factors only should at least for the 

 time being be suspended, in view of the discovery of the agent in some 

 mammary tumors appearing at an older age than 15 months ..." 



