12 V. ALEXANDER AND Z. M. BACQ 



when oxygen is admitted and this is due to the fact tliat the radicals 

 become pei'oxidized in both snljstances. Chemical analysis of irradiated 

 protein confirms that cystine is not preferentially destroyed (Alex- 

 ander and Hamilton, 1960). 



Deoxyribonucleic Acid {DNA) 



On quantitative grounds, DNA is a more likely candidate for the 

 primary lesion than enzymes, since it is probable that every molecule 

 is unique. It is possible therefore that damage to only a few molecules 

 per cell could affect survival. There are however a number of difficulties 

 with this interpretation (Alexander, 1900; Lett et a!., 1961a, b) and 

 before considering these we shall summarize the available information 

 about the chemical and physical changes that DNA undergoes on 

 irradiation. 



Indirect action. This results in far-reaching chemical changes such as 

 the opening up of the imidazole ring of the purines (Hems, 1960) and 

 the formation of jjeroxide groups on the pyrimidines (Ekert and 

 Monier, 1959). From the point of view of cell death (though not 

 necessarily for mutations) reactions that alter tlie macro-molecular 

 properties of DNA (such as main-chain scission or cross-linking) 

 are probably more important since every one of these is liable to 

 destroy the biological integrity of the molecule while isolated chemical 

 changes in one of the bases need not invariably be damaging. 



In dilute aqueous solution X-rays reduce the viscosity of DNA 

 (Taylor et al., 1948). This reaction is now known to be the result of 

 rupture of the molecule which occurs whenever a break has been j)ro- 

 duced in both of the constituent chains within a distance of some five 

 nucleotide units. A detailed investigation by Moroson and Alexander 

 (1960) has shown that for a DNA molecule of 5 x 10^ molecular weight 

 (number average) 65 OH radicals are necessary before a break becomes 

 apparent. The majority of the OH radicals are used up in producing 

 isolated (non-coincident) breaks that remain hidden. 



There has been a great deal of contradictory data concerning the 

 post-irradiation fall in viscosity of DNA following irradiation in dilute 

 solution, and complex mechanisms involving unstable peroxides and 

 phosphate esters have been proj)osed (see review given in Bacq and Alex- 

 ander, 1961). Although these reactions may occur to a limited extent, 

 two main causes for this in vitro post-effect have been found (Alexander, 

 1959). 



1. DNA is known to be unstable in solutions of low ionic strength. 

 If less than 10"^^ ]\([ of salt is present the molecule denatures on 



