422 RADIATION BIOLOGY 



ing sections, of conditions other than radiation which give rise to point 

 (or gene) mutations. 



If the view is held that some mahgnancies are caused by somatic 

 mutations, it might be expected that some carcinogenic agents (all those 

 which induced malignancies by this mechanism) would also prove to be 

 mutagenic. With this in mind Auerbach and the present writer in 

 1939-1940 planned a series of experiments to test the mutagenic effect 

 of methylcholanthrene and certain other carcinogenic hydrocarbons on 

 Drosophila. In these experiments, carried out by Auerbach, the carci- 

 nogen was introduced parenterally. The genetic testing was done on a 

 considerable scale. The results showed no perceptible increase in the 

 frequency of mutations inherited by the offspring of the treated as com- 

 pared with the control individuals. As was pointed out by Auerbach 

 (1940), however, these negative results do not necessarily indicate a dis- 

 junction between carcinogenicity and mutagenicity, even in this case, 

 since it is not known whether the given compounds or, indeed, any others 

 can induce malignancies in Drosophila, or even whether "true" malig- 

 nancies can occur in this organism, nor is it known whether the common 

 carcinogens undergo chemical reactions in insects which are at all similar 

 to those which they undergo in vertebrates. 



This stricture still applies to all such work on the mutagenicity, in 

 given nonvertebrates, of agents that are only known to be carcinogenic in 

 vertebrates. In fact, this criticism may now be made stronger. The 

 previously cited experiments with formaldehyde, for example, have given 

 direct evidence that the mutagenicity of a given agent may be narrowly 

 restricted to certain types of organisms ; so too have experiments showing 

 the mutagenicity of certain substances in bacteria and not in Drosophila. 

 It is therefore not to be wondered at, or regarded as an objection to the 

 somatic mutation interpretation of cancer, that, following Auerbach's 

 first work on the subject, all other really critical tests of the mutagenicity 

 of the carcinogenic hydrocarbons in nonvertebrate animals have given 

 negative results. We disregard here certain apparently (though Aveakly) 

 positive results, which were later shown to be nonreproducible (Demerec, 

 Wallace, Witkin, and Bertani, 1949). 



On the other hand, a much better test of the somatic mutation view 

 would be the determination of whether carcinogens capable of inducing 

 malignancies of varied kinds in vertebrates are mutagenic in the verte- 

 brates themselves. Unfortunately, however, the tests of this sort on 

 carcinogenic hydrocarbons which have so far been reported, although 

 claiming to be positive, have not been carried out with sufficient rigor on 

 the genetic side to give refiable results concerning mutation rate. On 

 vertebrate material, the required work would have to be very large-scale, 

 elaborate, and expensive, like, for example, that done on radiation 



