242 ERNST FREESE 



of absorlx^l I'licr^y, in roentgens, is the piopci- lucasui'c for the "dose." 

 Ho\ve\-(M', if the I'ffeetive lifetime of tiie pi'dduccil I'licinical (radic-ili is 

 short a hettei' nieasui'e foi' tlu^ dose would he tiie nuinher of ionizing parti- 

 cles whit'h penetrate the material, multiplied by some factor that 

 measures the ra(hation efficiency of these particles. These complications 

 arise only when one comi)ares radiations with different ionization densi- 

 ties. FarlieU's with high ionization density produce, per roentgen, more 

 chromosomal aberrations than particles with h)w ionization density, 

 probably because the chromosome has to be cut at more than one place; 

 in contrast the induction of mutations is usually more efficient for radia- 

 tions with low ionization density (Lea, 1955). 



This shows that the word "single hit" can mean different reactions. 

 It can mean a single chemical event or a single ionization, but it can 

 also mean a single cut by a densely ionizing particle. A single-hit curve, 

 without the precise knowledge of the chemical or physical reactions 

 going on, does not permit one to decide whether the reaction is direct 

 or indirect and how many chemical reactions occur until the actual 

 inactivating or mutating event takes place. 



The frequency of simple chromosome aberrations, e.g., deletions, is 

 proportional to the dose (measured in roentgens). Hence they arise by 

 "single hits." In contrast the more complicated ring dicentrics and ex- 

 change aberrations increase approximately with the square of the dose; 

 they are caused by two hits (Sax, 1957). The frequency of two-hit aber- 

 rations is larger when a certain dose is given continuously than when 

 it is fractionated, with larger rest periods. This indicates that chromo- 

 somal breaks have the chance to heal again and fewer aberrations are 

 produced when the healing takes place before the second hit occurs (e.g., 

 Sax, 1957). It is particularly interesting that anoxia (Wolff and Luip- 

 pold, 1955) as well as chloramphenicol (Wolff, 1959), an inhibitor of 

 protein .synthesis, keep the induced breaks open longer. These observa- 

 tions may have a significance for the understanding of the structure of 

 the chromosome as well as of mutation and recombination. 



The importance of the indirect radiation effect was recognized even 

 before the first chemical mutagens were known. Thus Fricke and 

 Demerec (1937) and Friedewald and Anderson (1940) showed that rab- 

 bit papilloma virus is about 20 times more resistant in crude preparations 

 than in a purified state. More light was shed on the indirect effect when 

 Thoday and Read (1947) found that low oxygen concentrations reduced 

 the frequency of chromosome breaks induced by X-radiation. This oxy- 

 gen effect has been extensively studied and it is jirobable that radiation 

 in the presence of oxygen causes tlie foi'mation of some peroxide radical 



