V. MOLECULAR MECHANISM OF MUTATIONS 243 



which in turn affects the frcciucncy of chromosome breaks and maybe 

 other mutations (see Stone, 1955). The formed peroxides may cause an 

 increase in the frequency of chromosome breaks either because they 

 induce breaks themselves or because they prevent the rejoining of 

 chromosomes cut by the radiation (Baker, 1955). Reducing agents lessen 

 the effect if added before the irradiation (Hollaender and Kimball, 1956). 

 The major effect of the peroxides is not known; one effect on DNA 

 could be the oxidation of the bases. In particular adenine readily reacts 

 with peroxides giving adenine-1-A^-oxide (Stevens et al., 1958; Frederik- 

 sen and Klenow, 1960), whose nucleotides are growth inhibitors. It is not 

 known whether the oxidation of bases in DNA is mutagenic. 



In microorganisms both forward and reverse mutations have been 

 induced by X-rays, e.g., in Neurospora (Giles et al., 1955), in bacteria 

 (Demerec and Sams, 1960), and in yeast (Gutz, 1961). The observations 

 prove that X-rays also often induce point mutations. 



Several phage strains are more readily inactivated in the absence 

 than in the presence of oxygen. Alper and Ebert (1954) conclude from 

 this and other irradiation experiments that phage is inactivated by re- 

 ducing rather than by oxidizing radicals. This may be due to an effect 

 on the phage protein rather than the DNA. (For a detailed review of the 

 radiation effect on vii-uses see Gard and Maal0e, 1959; Stahl, 1959). To 

 my knowledge there are no reports about the mutagenic effect of ionizing 

 radiations on free viruses. 



2. Ultraviolet Light 



The irradiation with UV has a more specific chemical effect than 

 ionizing radiation since the UV absorption is limited to molecules cariy- 

 ing conjugated double bonds and each of these molecules has a special 

 absorption spectrum with maxima at certain wavelengths. The absorp- 

 tion maxima of the nucleic acid bases are in the range of 260 to 280 m/x. 

 UV of this wavelength range exerts a strong direct effect on nucleic 

 acids. This can be seen especially well for viruses; they show no lethal 

 effect when they are introduced into preirradiated medium but are killed 

 by a single-hit curve when directly irradiated (McKinley et al., 1926; 

 Fisher and McKinley, 1927). The UV action spectrum of the rate of 

 inactivation has a maximum at 260 m/x indicating that the inactivating 

 "hits" occur directly in DNA. This is further supported by the observa- 

 tion that two or more UV-damaged phages can still infect the same bac- 

 terium and produce viable progeny (multiplicity reactivation, Luria, 

 1947). The ability of the phage to inject its DNA is inactivated much 

 more slowly than its viability. For one needs about 10 times as many 



