262 PHYSIOLOGIC GENETICS 



studies much more definitive. It also offers opportunities for studying the steps in the 

 development of neoplasia. It is hoped that the possibilities of this technique can be 

 pursued extensively to add to our knowledge of paths of genie action in development of 

 tumors. 



HOST-PARASITE RELATIONSHIP 



One of the paths through which genes can influence the occurrence of a neoplasm 

 is through their control over the propagation and transmission of an etiologic virus or 

 other parasite. Genetic effects can usually be demonstrated in the development of in- 

 bred strains that are susceptible and resistant to the virus or in the testing of existing 

 strains. 



Genetic control over the mammary-tumor virus was clearly demonstrated by 

 crossing susceptible strain C3H females that had the agent with resistant strain C57BL 

 males without the agent, and backcrossing the F x females all of which had the agent 

 with both susceptible strain G3H males and resistant strain C57BL males. 563 This 

 provided two groups of backcross females which differed genetically because of the 

 difference in their fathers but were alike in that they had received the virus from 

 genetically uniform F 1 females. The occurrence of more tumors in the test females 

 foster nursed by the C3H backcross females than in those foster nursed by the C57BL 

 backcross females indicated that the two backcross groups differed in their ability to 

 transmit the agent because of their differences in genotype. This study was later 

 extended to successive backcrosses to the resistant-strain males. By the third backcross 

 generation the agent was completely eliminated. 564 



In such studies the bioassay of the virus is extremely important. In the mammary- 

 tumor problem the presence or absence of the tumor is not proof of presence or absence 

 of the virus. Some females have the virus and do not develop tumors, and some tumors 

 develop in the absence of the virus. Electron-microscope pictures of particles are not 

 conclusive evidence alone. Even tests of prepared filtrates of tumors or other tissues 

 are not wholly satisfactory since viruses can be lost in the technical procedures. The 

 most reliable test for the presence of the mammary-tumor virus is the development of 

 tumors in females that have nursed upon the female being tested. 



One of the difficulties that can be encountered in a detailed genetic analysis is 

 that just as Kappa particles in Paramecium can be carried through several generations of 

 cells in the absence of the gene, 1256 so may cancer viruses be transmitted to immediate 

 offspring by females lacking the necessary genes for their propagation. This was found 

 to be true with the mammary-tumor virus, and in testing backcross segregants for their 

 genes controlling the propagation of the agent it was, therefore, necessary to observe 

 tumor occurrence not only in their offspring but also in test females that nursed upon 

 these offspring. The results of this study 571 clearly indicated that multiple genes were 

 involved in the propagation of the agent, and furthermore, that the quantity or quality 

 of the agent could be altered, presumably depending upon the number of these genes 



