340 H. B. ANDERVONT 



Heston (1958) and his colleagues (1956; Heston and Deringer, 1952) have 

 tried repeatedly to expose the virus in their virus-free substrain of C3H mice 

 but with negative results. Hybrids procured by reciprocal mating between 

 their C3H substrain and strain C57BL showed similar incidences of tumors; 

 if the C3H animals carried the virus, then their offspring should develop 

 more tumors than those derived from the agent-free C57BL mothers. One 

 exhaustive experiment consisted of outcrossing virus-carrying strain C3H 

 females to virus-free C57BL males and then backcrossing the female offspring 

 to C57BL males for seven generations. The virus was eliminated by the third 

 backcross generation. When the seventh backcross generation females were 

 bred to virus-free substrain C3H males and their female progeny backcrossed 

 to similar males for four generations, the concentration of strain C3H 

 chromatin did not bring about the reappearance of the virus. This showed 

 that the virus was not present in the last generation of backcross mice born to 

 C57BL fathers for, had it been present, the concentration of chromatin from 

 highly susceptible C3H males would have permitted it to increase in amounts 

 sufficient to produce tumors. Finally, a thorough analysis of the tumors 

 occurring in the virus-free substrain gave no indication of the presence of the 

 virus. For example, females with three successive generations of tumors in 

 their immediate maternal ancestry did not develop more tumors than those 

 with tumor-free ancestors. Instead, analysis revealed a correlation between 

 the numbers of litters the females bore and their incidences of tumors. 



Andervont and Dunn (1958) have continued their studies with hybrids by 

 the administration of estrogenic stimulation to castrated males derived from 

 virus-free parents. Some groups of these male hybrids showed tumor incidences 

 ranging from 59 to 84 % at average ages of 12 to 14 months and, as in the 

 earlier work, hybrids most susceptible to the estrogen-induced tumors were 

 derived from inbred strains which were most susceptible to the virus; hybrids 

 with a strain C3H parent were among the most susceptible. 



Boot and Miihlbock (1956) have reviewed the literature dealing with the 

 production of mammary tumors in virus-free inbred mice and have presented 

 their findings with virus-free strain C3H animals. They arrived at the conclu- 

 sion that the occurrence of mammary tumors in these mice resulted from a 

 combination of hormonal stimulation and a high susceptibility to mammary 

 cancer and, "the only logical explanation of this susceptibility seems to be to 

 consider it as an expression of the genetic constitution of the agent-free C3H 

 substrains." Miihlbock (1956), in a recent review of the hormonal genesis of 

 mammary cancer, records the production of mammary tumors in virus-free 

 mice of strains C3H, DBA, O 20 , and C57BL by subcutaneous transplantation 

 of hypophyses. The successful induction of mammary tumors in virus- 

 resistant C57BL animals is conclusive evidence that these tumors do arise in 

 the absence of the virus. 



