170 MICHAEL FELDMAN AND DAVID YAFFE 



taking place within the tumour cell population while growing in 

 the radiation chimera. However, while transplantation tests in 

 normal animals showed that the SBLi is more susceptible to the 

 homograft reaction than the MCiM (see Feldman and Sachs, 

 1957), the MCiM was rejected by the "foreign" spleen cells of 

 the chimera, whereas the SBLi was not. This made the second 

 assumption — the possibility of changes induced in the immuno- 

 genetic properties of tumour cell populations — more feasible, and 

 experiments were performed to test this. 



Sarcoma SBLi was grafted to C3H foetal-cell treated 

 chimeras, and both the tumour of the original transplant and that 

 of the lymph node metastasis were removed and tested for 

 transplantability in normal homologous hosts. The results 

 (Fig. i) showed that following one transplant generation of SBLi 

 within the C3H chimeras, a change takes place in the tumour cell 

 population, which was manifested in 20-50 per cent lethal takes 

 of the tumours in non-irradiated secondary hosts. Further serial 

 transfers through 3-4 transplant generations estabhshed homo- 

 transplantable tumour lines (SBLx sublines), which gave 100 per 

 cent lethal takes in foreign hosts. The homotransplantability 

 acquired by tumour cell populations in C3H chimeras, and then 

 selected out in C3H normal hosts, showed no strain-specificity: 

 the SBLx sublines established in C3H animals gave lethal takes 

 in animals of H-2D, H-2K, H-2B and H-2S genotypes. 



Such changes, manifested in an acquired homotransplantabihty 

 of a strain-specific tumour, were repeatedly obtained with 

 sarcoma SBLi. In order to obtain some insight into the 

 mechanism of induction of the loss of strain-specificity, we 

 attempted to test (i) the immunogenetic factors in the chimera 

 which control or influence such changes, and (2) the properties 

 acquired by the "changed" tumour cell population which make 

 possible the progressive growth of the tumour in genetically 

 foreign hosts. 



Some years ago, Koprowski, Theis and Love (1956) described 



