The Journal of Heredity 



gene that might he present nearby in a 

 homologous chromosome. 



Radiation-Effects 



In addition to the individual gene 

 changes, radiation also produced rear- 

 rangements of parts of chromosomes. 

 As our later work (including that with 

 co-workers, especially Raychaudhuri and 

 Pontecorvo) has shown, these latter 

 were caused in the first place by hreak- 

 ages of the chromosomes, followed after- 

 wards by attachments occurring hetween 

 the adhesive broken ends, that joined 

 them in a different order than before. 

 The two or more breaks involved in 

 such a rearrangement may be far apart, 

 caused by independent hits, and thus re- 

 sult in what we call a gross structural 

 change. Such changes are of various 

 kinds, depending upon just where the 

 breaks are and just which broken ends 

 become attached to which. But, though 

 the effects of the individual "hits" are 

 rather narrowly localized, it is not un- 

 common for two breaks to be produced 

 at nearby points by what amounts to 

 one local change (or at any rate one lo- 

 calized group of changes) whose influ- 

 ence becomes somewhat spread out. By 

 the rejoining, ; n a new order, of broken 

 ends resulting from two such nearby 

 breaks, a minute change of sequence of 

 the genes is brought about. More usual- 

 ly, the small piece between the two 

 breaks becomes lost (a "deficiency"), 

 but sometimes it becomes inverted, or 

 even becomes transferred into a totally 

 different position, made available by a 

 separate hit. 



Both earlier and later work by collabo- 

 rators (Oliver, Hanson, etc.) showed 

 definitely that the frequency of the gene 

 mutations is directly and simply propor- 

 tional to the dose of irradiation applied, 

 and this despite the wave length used, 

 whether X- or gamma or even beta rays, 

 and despite the timing of the irradiation. 

 These facts have since been established 

 with great exactitude and detail, more 

 especially by Timofeeff and his co- 

 workers. In our more recent work with 

 Raychaudhuri these principles have 

 been extended to total doses as low as 



400r, and rates as low as .01 r per min- 

 ute, with gamma rays. They leave, we 

 believe, no escape from the conclusion 

 that there is no threshold dose, and that 

 the individual mutations result from in- 

 dividual "hits", producing genetic ef- 

 fects in their immediate neighborhood. 

 Whether these so-called "hits" are the 

 individual ionizations, or may even be 

 the activations that occur at lower ener- 

 gy levels, or whether, at the other end 

 of the scale, they require the clustering 

 of ionizations that occurs at the termini 

 of electron tracks and of their side 

 branches (as Lea and Fano point out 

 might be the case), is as yet undecided. 

 But in any case they are, even when 

 microscopically considered, what we 

 have termed "point mutations," as they 

 involve only disturbances on an ultra- 

 microscopically localized scale. And 

 whether or not they are to occur at any 

 particular point is entirely a matter of 

 accident, using this term in the sense in 

 which it is employed in the mathematics 

 of statistics. 



Naturally, other agents than photons 

 which produce effects of this kind must 

 also produce mutations, as has been 

 shown by students and collaborators 

 working under Altenburg in Houston 

 for neutrons (Nagai and Locher) and 

 for alpha rays (Ward) and confirmed 

 by Timofeeff and his co-workers (Zim- 

 mer, et al). Moreover, as Alten- 

 burg showed, even the smaller quan- 

 tum changes induced by ultraviolet exert 

 this effect on the genes. They cause, 

 however, only a relatively small amount 

 of rearrangement of chromosome parts 

 (Muller and Mackenzie), and, in fact, 

 they also tend to inhibit such rearrange- 

 ment, as Swanson, followed by Kauff- 

 mann and Hollaender. has found. Since 

 the effective ultraviolet hits are in the 

 form of randomly scattered single-atom 

 changes in the purines and pyrimidines 

 of the chromosome, rather than in 

 groups of atom changes, it seems likely 

 that clusters of ionizations are not neces- 

 sary for the gene mutation effects, at any 

 rate, although we cannot be sure of this 

 until the relation of mutation frequency 

 to dosage is better known for this agent. 



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