L. n. (;rav 



not, of course, inipl) that when a mutation occurs at a given locus the energy 

 suppHed by the ionizing radiation itself induces a switch between alternative 

 molecular configurations. It is equally possible, and rather more in keeping 

 with the phenomenon of multiplicity reactivation in viruses, to assume that in 

 the case of both forward and back mutation a molecular configuration which 

 has been rendered defective by irradiation, may be replaced at the time of the 

 gene reduplication by one of a limited number of possible alternative con- 

 figurations representing the alleles at the locus in question. The nature of the 

 original defect remains to be discovered. 



Damage to the Genome — Visible 

 Structural damage to chromosomes has a three-fold chance of detection, 

 namely by genetic analysis, by microscopic observation at metaphase and 

 anaphase, and by the fact that it generally impairs the proliferative capacity 

 of the cell. Accordingly, it is one of the best documented forms of radio- 

 biological damage. Other organelles may be damaged as frequently as 

 chromosomes, but escape notice for want of visual or functional methods 

 of detection. In fact, mitochondrial damage may be prominent at an early 

 stage in irradiated cells. Thus, Ludford^ reports that 40 min after a mouse 

 adenocarcinoma 27 had been exposed in vivo to mixed ^ and y radiation, the 

 mitochondria of almost every cell were either granular or vesicular, and in 

 some cells were reduced in numbers. The dose is, unfortunately, not known 

 but was probably between 500 and 1500 rad. At this time the chromosomes 

 of the very few cells which were in division were showing signs of stickiness 

 and clumping. Chromosome structural damage would only have become 

 microscopically visible very much later, after the period of mitotic inhibition, 

 which lasted more than a day in these cells under the particular conditions 

 of irradiation used by Ludford. Despite the earlier appearance of the 

 mitochondrial damage, we can be much less certain of its relation to primary 

 disturbances than in the case of chromosome structural damage. At the 

 levels of dose with which we are concerned, neither form of damage would be 

 visible in cells in which metabolism had been in abeyance between irradiation 

 and the time of observation. Both may therefore, in principle, be regarded 

 as a manifestation of the response of the cell to injuries outside the organelles 

 concerned. In the case of chromosome structural damage, however, dose and 

 dose-rate relations observed with radiations of differing LET, as well as the 

 agreement between the observed distribution of aberrations between the 

 cells of an irradiated population with that expected for random events, 

 indicates that each observed aberration has been initiated by a monotopic 

 event. These relations also indicate that aberrations which involve two 

 chromatids are only formed when events are initiated either by one ionizing 

 particle, or by two, at adjacent sites in each of the two threads. Finally, the 

 very beautiful micro-beam experiments of Bloom, Zirkle, and Uretz"* have 

 shown that the probability of producing a chromosome aberration by the 

 passage of a proton through other organelles, or through the cytoplasm at 

 several microns distant from a chromosome, is negligible compared with a 

 probability that an aberration will be initiated by a proton which passes 

 through, or in the immediate vicinity of, the site at which the aberration 

 subsequently appears. 



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