376 



CELL HEREDITY 



Azaserine 



4 6 8 10 12 



Transfer Generation 



FIGURE 12.11. Selection of resistant forms of mouse tumors in the presence of in- 

 creasing concentrations of drugs (from Law, 1958, Ann. N. Y. Acad. Sci., 71:976). 



less, provided the nutrients required. Later, better defined media con- 

 taining macromolecular serum fractions and growth factors such as 

 cholesterol and vitamin C were found to support the growth of all the 

 single cells plated. These cells may come from many sources, and upon 

 plating new clones can be established. The chromosome number may 

 be euploid, or, if not euploid after the establishment of the clone, it 

 can be made to remain essentially constant under certain conditions. 



Monodispersed cultures of human cells have a genetic stability re- 

 sembling that of bacteria, but variants do occur despite constancy in 

 chromosome composition. Among them are types with changed nutri- 

 tional requirement, growth rate, morphology, surface properties, and 

 drug and virus sensitivity. For example, a change from a type con- 

 sisting of polygonal cells in a compact colony to fusiform types forming a 

 loose colony occurs at a rate of ca. 8 x 10~^ per cell per division. The 

 fusiform type, unlike the polygonal type, is refractory to infection by 

 polio virus and can be selected without exposure to the virus because of 

 its different morphology. This shows the spontaneous origin of this trait. 

 In another case, the fluctuation test of Luria and Delbriick was em- 

 ployed to show that resistance to A-methopterin by leukemia tumor cells 

 was not induced by the drug (Table 12.2). Variation and selection 

 brought about the change. The same seems true of the transformation 

 of solid tumors into ascites cells which grow freely in the fluid of the 

 body cavities. In one experiment when an average of 4.3 cells producing 

 solid tumors were implanted, 7 out of 8 transfer lines gave rise to ascites 



