264 PHYSIOLOGIC GENETICS 



can be done best in the lower organisms which, with few exceptions, are not suited to 

 carcinogenic studies, whereas the carcinogenic tests should be made in the mouse or 

 rat which are not well suited to mutagenic tes's. 



Statistical studies of dose-response curves have been of some interest. Charles 

 and Luce-Clausen 197 found that data on response of mice to repeated painting of a 

 carcinogen on the skin measured in number of induced papillomas gave an exponential 

 curve which they suggested was what would be expected were the neoplastic change 

 due to a recessive mutation. However, our data 568 on number of pulmonary tumors 

 induced in strain A mice with graded doses of dibenz[a, A] anthracene indicated a 

 straight line response which would suggest a single event, and if this were a genie 

 mutation then it must be dominant. 



It would seem that now the way may be opened for an attack on this problem 

 through techniques of tissue culture. With the single-cell cloning techniques now 

 perfected 1026 ' 1149 and with chemically defined media now in use, 329, 330> 1359 genetic 

 nutritional changes in cells can be identified. By using cells from one of the highly 

 inbred strains so that the point at which they become malignant can be determined by 

 successive transplantation of the cultured cells back into the strain of origin, it may be 

 possible to associate some of these nutritional changes with the neoplastic change. 



DISCUSSION 



Dr. Andervont: Those who have worked in cancer research during recent years 

 recognize the importance of inbred animals that have proved so invaluable. They are 

 used to ascertain the response of different inbred strains to a standard dose of carcinogen 

 or the response of a single strain to graded amounts of a carcinogen. In essence, 

 geneticists have made possible a quantitative approach to the problems of the relation- 

 ship between host and cancer-inciting factors. This contribution alone is sufficient to 

 justify the use of inbred animals, but, as Dr. Heston has pointed out, cancer is a complex 

 disease. 



He used mammary cancer of mice to exemplify this complexity because it is an 

 excellent example of the reactions of the host to a combination of genetic, viral, and 

 environmental influences. Geneticists have given most of their attention to the host, 

 with the result that the most clearly defined factor in the occurrence of the disease is 

 the genetic constitution of the host. Their efforts have yielded important contribu- 

 tions, such as the discovery of the mammary-tumor agent, but they have also un- 

 covered many new problems. The inbred strains display a remarkable difference in 

 susceptibility to the virus as well as to the production of breast cancer by hormonal 

 stimulation in the absence of the virus. It is of some interest that, according to evidence 

 now available, those strains susceptible to hormone-induced breast cancer are also 

 susceptible to the virus. This does not imply that all strains susceptible to the virus are 

 also susceptible to hormone-induced tumors, but only that those which respond readily to 

 the administration of estrogenic hormones are also susceptible to the virus. 



