424 RADIATION BIOLOGY 



mutations in organisms in general should in addition prove to be carcino- 

 genic in vertebrates. Thus the recent finding of chemical mutagens has 

 furnished an unexampled opportunity for the further testing out of the 

 hypothesis along these lines. 



For a long time it had been thought that chemicals of the mustard 

 group were not carcinogenic. However, more adequate tests, recently 

 carried out at the Chester Beatty Research Institute in England (Bird, 

 1949, 1950; Boyland and Horning, 1949), at the U. S. Institutes of Health 

 (Heston, 1949, 1950) and at Stanford University (Griffen, Brandt, and 

 Tatum, 1950) have now left no doubt of the efficacy of nitrogen mustards 

 and of other mutagenic mustards in inducing malignancies of varied 

 kinds. Moreover, as for urethane, it has long been known that this sub- 

 stance is carcinogenic. This striking series of correspondences can hardly 

 be dismissed as mere coincidence, and therefore serves greatly to 

 strengthen, if not actually to clinch, the argument for the mutational 

 interpretation.^ Fortunately, however, for the removal or confirmation 

 of residual doubts, the way is still open for the ready extension of this 

 line of investigation by the testing of the carcinogenicity of other sub- 

 stances for which evidence of a generalized mutagenicity is obtained. 

 Moreover, it still remains to be determined whether conditions which, 

 when acting along with mutagens, under all circumstances increase or 

 decrease the efficacy of the latter in mutagenesis, have a corresponding 

 influence on their carcinogenic potency also. 



On returning to the original question of whether the effect of radiation 

 in producing gene mutations forms the basis of its effect in producing 

 malignancies, it will be seen that a comparative survey of the results not 

 only with radiation of different types but also with other agents now 

 makes this view- — better, in the light of these results, to be termed a 

 theory — highly probable. 



20. MANNER OF ACCUMULATION, EXPRESSION, 

 AND ELIMINATION OF MUTATIONS 



Gross structural changes of chromosomes involving translocations 



or gross inversions usually result (as pointed out in Sects. 5-6) in a 



^ At the same time, the above conclusion in no way casts doubt upon the fact, long 

 since demonstrated, that some maHgnancies are caused not by gene mutation but 

 by the influence of parasitic microorganisms or viruses, some of which may under other 

 circumstances or when possessed of a somewhat different genetic composition be non- 

 maUgnant or even symbiotic. It is in addition possible, although at present in the 

 realm of speculation, that in some cases changes in plasmagenes, or in autocatalytically 

 replenished substances originating in the organism itself [like the antigens studied by 

 Sonneborn (1948, 1950) in Paramecium], iorm the basis of malignancies. The chromo- 

 somal genes of the organism itself, however, by virtue of their number, variety, and 

 stability in transmission through cell division, afford the greatest amount of diversity, 

 range of effect, and material for the accomplishment of such changes. 



