448 GENETICS OF SOMATIC CELLS 



with the same virus. In cultures of cells from the mouse, the cytocidal interaction 

 was most frequent, while in cultures of cells from the hamster the moderate interaction 

 was almost exclusive. They explain these results by the following hypothesis : "Upon 

 entering a cell, the virus assumes an ' uncommitted ' state in both hamster and mouse 

 cells, during which it may undergo a limited multiplication without appreciably affect- 

 ing the normal properties of the cell. From this 'uncommitted' state, the virus has the 

 choice of entering either the state of cytocidal multiplication or the integrated state. 

 The late transformation of the mouse cultures would be due to the selection of a few 

 transformed cells. In the hamster cultures, on the other hand, the choice would be 

 almost exclusively toward the integrated state, both in the animal and in the tissue 

 culture." 1350 As to the state of the virus in the transformed cells, the absence or low 

 level of production of virus and the resistance to superinfection were similar to the pro- 

 perties of lysogenic bacterial culture, suggesting that the integrated virus exists as a 

 provirus. However, as Vogt and Dulbecco pointed out, other explanations are not 

 excluded, and it is conceivable that the virus could ultimately be lost from the trans- 

 formed cells and resistance to superinfection might be a secondary consequence of trans- 

 formation. 



It is obviously of the greatest interest to investigate the relationship between viral 

 and cellular genome more extensively, not only because of its significance for the under- 

 standing of relationships between virus and cell in general and viral oncogenesis in 

 particular, but also from the point of view of somatic-cell genetics. Provided that a 

 truly integrated state really exists, it may permit the development of methods for genetic 

 transfer such as already exist in microbiology in the form of transduction and lysogenic 

 conversion. 



Some general considerations. — To close this section on neoplastic cell populations 

 in vivo, it has to be emphasized that the variability of such markers as isoantigens or 

 drug resistance does not necessarily reflect any tumor-specific property. Comparable 

 information on normal cells in vivo is not available. Neoplastic cells represent special 

 types of somatic cells and while certain markers may display a similar variation in com- 

 parable normal and neoplastic tissues, others may not; this will have to be established 

 from case to case. For instance, it is not known whether normal bone-marrow cells 

 can develop resistance against antileukemic antimetabolites in the same way as leukemic 

 cells do. With leukemic cells, serial transplantation in the presence of the drug is often 

 necessary to establish a line resistant to a given compound. Only seldom does resistance 

 become apparent in the course of treatment in the first host, which is usually killed by 

 the background growth of sensitive cells. 447 Bone-marrow cells would have to be exposed 

 under the same conditions, that is, during serial transfer, in order to investigate whether 

 they can become resistant or not. Such serial transfer is quite feasible through lethally 

 irradiated mice; the marrow cells remain normal and do not become leukemic under 

 such conditions. 385 This system would also permit the study of isoantigenic variation 

 in bone-marrow cells in experiments similar to those carried out with various types of 

 neoplastic cells. Another approach would be to compare isoantigenic variation in 



