MUTATION AS A CHEMICAL PROCESS 229 



are present, the inhibitor of protein synthesis, chloramphenicol, prevents 

 their effect. Furthermore, the formation of abnormal protein containing 

 amino acid analogues decreases the mutant yield. Consequently, protein 

 synthesis seems a prerequisite for DNA formation and, as a result, for 

 mutation. These effects on mutation can be observed only during the 

 initial part of the first postirradiation division whose length can be 

 increased by the dose of ultraviolet light and by nonmutagenic concen- 

 trations of caffein, which inhibit DNA synthesis. After this division the 

 primary effect of ultraviolet light on the cell, perhaps a pool of modified 

 DNA precursors, has been dissipated. 



Protein synthesis is not the only process that is prerequisite for DNA 

 formation and mutation; its concomitant, RNA synthesis, is also required. 

 A turnover of RNA precedes DNA synthesis in phage-infected bacteria. 

 Furthermore, the role of RNA can be shown by the use of inhibitors and 

 the starvation of uracilless auxotrophs after irradiation. In cells so 

 treated, DNA synthesis is not restored until RNA synthesis is permitted 

 again. 



But what can DNA synthesis do to establish the mutation? Ultra- 

 violet light, like other radiations, induces chemical modifications in sub- 

 stances that absorb it. Some, including water and amino acids, are 

 converted into highly reactive free radicals and peroxides which are 

 mutagenic, but many of these products are unstable or are decomposed 

 by the cell before they can act. When adenine, guanine, cytosine, uracil, 

 or their ribosides are given to bacteria just before irradiation, the yield 

 of mutants is increased. When these substances are irradiated by them- 

 selves, they form unstable products. It may be that the immediate effect 

 of UV-irradiation is the modification of nucleic acid precursors. The 

 synthesis of protein and RNA may be necessary for the incorporation of 

 such modified precursors into DNA and for its subsequent replication 

 which completes the change of genotype. 



Thus we should think of mutation as quite different from the spon- 

 taneous disintegrations of radioactive atoms which obey monomolecular 

 kinetics and are independent of environmental conditions. This is true 

 also of spontaneous mutations; not only are they reversible but also in 

 other ways their properties are those of biochemical processes. For 

 example, spontaneous mutations usually have a Q^q of 2 or 3, as is 

 shown in Figure 8.18. The fact that spontaneous mutations do not occur 

 at temperatures as low as 0° (although the cells survive) indicates that 

 they are not, for the most part, induced by local molecular agitation 

 which, with a low frequency proportional to temperature, would involve 

 energies high enough to induce a rare chemical change in the gene. If 



