212 



CELL HEREDITY 





50 



100 



150 

 Time, Hours 



200 



250 



FIGURE 8.5. Simulacreof the effect of adenosine on adenine-induced and spontaneous 

 mutation of bacteria in the chemostat (after Novick and Szilard, 1952, Nafure, 

 170:927). 



tion, it has been shown in bacteria that growth and division, with 

 the inevitable DNA synthesis that accompanies them, are prerequisite 

 for the mutagenic action of purine analogues. One of these, 2-amino 

 purine, induces mutations while DNA is replicating but not after it has 

 nearly ceased (Figure 8.4). Furthermore, when the purine, caffein, is 

 used as a mutagen, its effect can be shown to be decreased by chloram- 

 phenicol during the first few hours of treatment in proportion to the 

 decrease in the rate of DNA synthesis that occurs. It seems, then, that 

 unusual purines and purine analogues, if they are not incorporated them- 

 selves, somehow affect the incorporation of bases into newly synthesized 

 DNA; as a consequence, replication is necessary before the mutations 

 can occur. 



INCORPORATION OF UNUSUAL NUCLEOTIDES AND COPY ERRORS 



Some studies on mutation made in the chemostat have shown that 

 purines, such as caffein and adenine, are mutagenic when they are con- 

 tinually supplied to the medium, while some ribosides, such as adeno- 

 sine and guanosine, can reverse this effect. Adenosine even reduces 

 spontaneous mutation in the absence of adenine, but it cannot eliminate 

 it entirely (Figure 8.5). Therefore, we know that there are likely to be 

 at least two mechanisms for spontaneous mutation. The one that is 



