238 H. J. MULLEE 



ways those of known chromosome breaks (to be considered presently). 

 However, inasmuch as the proposed inactivations took place in non-dividing 

 as well as in dividing groups of cells, this interpretation would be contradicted 

 by the massive evidence showing the far greater radiation damage done to 

 proliferating than to non-proliferating tissues. One striking example in point 

 here is the enormously higher dose required to produce a given shortening of 

 the life-span when irradiation is applied to adult insects which have virtually 

 no cell divisions than when applied to their earlier stages. As for spontaneous 

 ageing, the diverse arguments already given against this process being based 

 in genetic changes apply equally to views which regard these changes as 

 as point-mutational and as inactivations or losses of whole chromosomes or 

 chromosome regions. 



In an analysis of the process of structural change in Drosophila the present 

 author (1940) advanced the view that, in general, except for the production 

 of cancers (which are probably of point-mutational nature) the damagmg 

 effects of radiation noted in somatic tissues are the results of chromosome 

 breaks. Moreover, he extended this interpretation to include radiation- 

 induced life-span shortening (1950) shortly after the discovery of this 

 phenomenon had been made known. There were, however, two possible 

 variants of this interpretation since genetic studies of the events in germ cells 

 and in the divisions following fertilization in Drosphila had shown that chromo- 

 some breaks, when not followed by exact restitution, can act in two different 

 ways to cause the death of daughter-cells or of zygotes derived from them. 



In the first case, found to be more usual for most cells, the broken 

 chromosome or chromosomes fail to become incorporated in the nucleus of a 

 daughter-cell because the pieces have joined together so as to given rise on the 

 one hand to acentric pieces, those lacking any centromere to mediate their 

 transportation to the poles, and/or, on the other hand, to dicentric pieces, 

 having two centromeres that pull in opposite directions. This can happen 

 even in consequence of single chromosome breaks, which are produced at a 

 rate proportional to the dose (Muller, 1940; Pontecorvo, 1941), for in such 

 cases the two chromatid fragments derived by replication (either before or 

 after the break) from the acentric chromosome fragment may unite at their 

 broken ends to form an acentric isochromosome, as it is called, while the two 

 chromatid fragments derived from the chromosome fragment having the 

 centromere, on uniting similarly, form a dicentric isochromosome that; fails to 

 reach either pole. If, now, the missing chromosome material were essential to 

 life, as in the case of the single X-chromosome of a male cell or any chromo- 

 some of a haploid ceU, the resulting hypoploid cell or zygote would die. This 

 method of killing would obviously be less damaging to cells of higher ploidy. 



In the case of the other mode of death, the pieces join up in the same way 

 as already described. However, the dicentric structure, instead of being left 



