480 RADIATION BIOLOGY 



2. CHROMOSOME BREAKAGE 



AND GROSS REARRANGEMENT FREQUENCY 



IN RELATION TO AMOUNT AND DISTRIBUTION OF IONIZATIONS 



Chromosome breaks, like point mutations, are produced with a fre- 

 quency simply proportionate to the total dosage of ionizing radiation 

 applied. However, the frequency of gross structural changes varies as a 

 power of the dose higher than 1 when X or 7 rays are applied in ordinary 

 doses, since with such irradiation the broken ends which unite are usually 

 produced by independently arising breaks, and the products, the struc- 

 turally changed chromosomes, therefore represent a concatenation of 

 effects. Evidence for these conclusions, which correspond with the 

 ''breakage-first" theory first definitely advocated by Levitsky and 

 Araratian (1931) and by Stadler (1932), was obtained through two differ- 

 ent series of investigations. One of these was carried out by Muller and 

 his co-workers in studies on the effects of radiation on mature Drosophila 

 spermatozoa, by the use of genetic methods of analysis, and the other 

 was carried out first by Sax and by Faberge on plant material, using 

 cytological methods. 



In the Drosophila work, evidence that at least some of the different 

 breaks involved in a given structural change are produced by independent 

 hits had first been gained in experiments, conducted in 1933 by Muller, 

 Koerner, and M. Vogt and announced- in 1935, on the frequency with 

 which large deletions of the X chromosome are produced; this frequency 

 was found to vary as a distinctly higher power of the dose than 1 , namely 

 as the ^'2 power. Studies of this type were soon afterward made on 

 translocations by Belgovsky (1937), working under Muller's direction, 

 and on inversions by Berg, Panshin, and Borisoff (cited by Muller, 1936a, 

 1937, 1938). The same ^^-power rule was observed for both transloca- 

 tions and inversions as had been found for deletions. It was confirmed in 

 more extensive studies on translocations conducted by Sidky, Ray- 

 Chaudhuri, Makki, and Makhijani, working in collaboration with Muller 

 (see Muller, 1938, 1939a, b, c, 1940; Muller, Makki, and Sidky, 1939; 

 Makhijani, 1945). 



It is true that certain authors, notably Dubinin and his co-workers 



(Dubinin and Khvostova, 1935; Demidova, 1937; Khvostova and 



Gavrilova, 1935, 1938), Catcheside (1938), and Eberhardt (1939), 



obtained results which they regarded as indicating a linear relation 



between the dose and the frequency of gross structural changes. In some 



2 The data on deletions, as well as those on translocations, showing the %-power 

 relation, were presented by Muller and Belgovsky at a meeting of geneticists held at 

 the Institute of Genetics, Moscow, in 1935, and are first referred to in the literature by 

 Dubinin and Khvostova (1935), Muller (1936a, 1937, 1938), and Kirssanow (1937). 

 The data on translocations were published by Belgovsky (1937) and those on deletions 

 by Muller (1938). 



