GENETICS OF NEOPLASIA 265 



In contrast, there is no well-defined correlation between susceptibility to the virus 

 and susceptibility to chemically induced tumors. For example, mice of strain DBA/2 

 are susceptible to both virus and chemically induced breast tumors, whereas those of 

 strain IF are resistant to the virus but susceptible to a chemical carcinogen. As Dr. 

 Heston stated, strain C3H mice are susceptible to both virus and hormone-induced 

 tumors but resistant to carcinogen-induced tumors. These striking variations in 

 susceptibility to induced breast tumors raise the problem of whether we are dealing 

 with a single disease or different diseases. If mammary cancer in mice is classified 

 according to its etiologic agent, then we are dealing with different diseases. 



Hepatoma arising in mice, too, is the result of the interplay of several factors. A 

 virus has not been implicated but, as Dr. Heston described, heredity is very important. 

 Hormonal influences are involved because the spontaneous tumors occur more fre- 

 quently in males of all inbred strains susceptible to their development. Diet exerts a 

 pronounced influence on their development. 



Experiments performed with strain C3H mice as test animals reveal the com- 

 plexity of these tumors. Males develop more spontaneous tumors than do females, 

 but when the tumors are induced by the administration of an azo dye the females are 

 far more susceptible than males. However, castrated males are as susceptible as 

 females and can be made resistant again by injection of androgens. When tumors are 

 induced by the administration of carbon tetrachloride, both sexes appear to be equally 

 susceptible. However, a single strain of inbred mice exhibits remarkable variation 

 in susceptibility to this tumor. Such variations suggest to the oncologist that he is 

 dealing with a group of diseases which eventuate in the same final manifestation. At 

 least the tumor can be studied within a single inbred strain when the genetic factor 

 remains constant. 



Any discussion of Dr. Heston's paper would be incomplete without some mention 

 of the contribution the methodology of genetics has made to recent advances in the field 

 of tumor viruses. During the past seven years at least six viruses have been implicated 

 in the origin of leukemia, or leukemia-like lesions, in laboratory mice. To those 

 attending this symposium the interesting feature of these viruses is their range of 

 specificity for inbred strains of mice. Much work remains to be done along these lines, 

 but, to date, strain DBA is susceptible and strain C3H is resistant to one virus, whereas 

 all strains tested thus far are susceptible to another. These two viruses represent the 

 extremes of the six. 



You will recall that the murine mammary-tumor agent varies in concentration in 

 different strains but that a susceptible strain reponds to the virus from other strains. 

 If the specificity of the leukemia virus for certain strains is established firmly by future 

 studies, then the establishment of inbred strains will have enabled the virologist to 

 detect tumor viruses specific for certain genetic constitutions within a species. Carrying 

 this thought one step further, it is possible that, within a genetically heterogenous 

 species, some tumors are induced by viruses which are so specific that they produce 

 tumors only in certain individuals. On the other hand, the ability of murine leukemia 



