GENETICS OF NEOPLASIA 261 



tumors. In testing their own second-backcross offspring, however, it was found that 

 certain ones of these first-backcross females did not have any offspring that could 

 transmit the agent. It thus appears the C57BL females and certain backcrosssegregants 

 lack the genes for propagation of the agent and although they do not eliminate what 

 agent they receive, it does not multiply and is lost completely (presumably by dilution) 

 in the subsequent generation. 



Dr. Klein : I read the paper and was quite convinced the agent was lost, but I was 

 not sure whether the agent was lost because it lacked something in the host or because 

 it was eliminated by a host reaction. Can you distinguish between these two 

 possibilities ? 



Dr. Heston: I think it is lost from some process like being diluted out and not 

 by being destroyed by the animal. 



Dr. Yerganian: With respect to Dr. Heston's remarks concerning the role of 

 underlying variables, an interesting sequence of events has taken place since 1954, when 

 we provided the Chester Beatty Institute with a subline of partly inbred Chinese 

 hamsters having then undergone four generations of inbreeding. Shortly thereafter, 

 this new colony provided a subline to the Radiobiological Research Unit at Harwell. 

 I have been informed by Dr. C. E. Ford that the subcolony at Harwell is now in the 

 thirteenth generation of brother-sister matings and has developed an extensive number 

 of pituitary and pancreatic carcinomas among both the control and X-irradiated 

 populations. In our hands, the parental line (BUY) is now in the seventeenth genera- 

 tion and has a relatively high incidence (7 per cent) of diabetes mellitus by 200 days of 

 age. 



I was wondering if genetic drift would have any underlying contributions towards 

 this presumably unrelated dichotomy and, if so, whether or not cancer may then be 

 regarded as a form of metabolic dysfunction which, in the Harwell colony, is expressed 

 in a malignant pattern, whereas a slight alteration in the genetic complex in question 

 within the Boston colony is expressed metabolically as diabetes mellitus. In both 

 instances, the target cells and organs are identical. 



Dr. Chai : I am in agreement with Dr. Heston's concept that tumors are threshold 

 genetic characters. To this I should like to add (as a speculation) that development of 

 tumors depends not only on genes with major effects but also on the genetic background 

 and interaction between the genes. There are many published data which can be so 

 interpreted. For instance, there were differences in incidence of mammary tumors 

 between the F \ and F 2 hybrids in crosses involving cancerous strains of mice. 793 These 

 differences can be explained by the threshold concept as the level of threshold fell on 

 certain points in the frequency distributions of the genotypes. They can also be 

 explained by the differences in genetic background and possibly by different inter- 

 actions between the genes. There are many threshold characters, including some 

 hereditary diseases and deformations, for which the incidences are different on different 

 backgrounds, and the genetics is complex and not all clear. Most of the tumor data 

 in experimental animals come from highly inbred and not from noninbred animals. 



