auerbach: effects of chemicals 133 



The Production of Specific Genetical Changes 



From its early stages, work with chemical mutagens brought 

 evidence for the possibility that these substances might be more 

 specific than X-rays in their effects on the genetic material. Dur- 

 ing many years, however, the detectable specificity Avas regional 

 rather than genie. The distribution of chemically induced chromo- 

 some breaks in plants was found not to be random (38, 51, 72, 75). 

 After treatment with certain chemicals, it was highly localized (23). 

 Most chemicals appear to produce more breaks in heterochromatic 

 than euchromatic regions. In Drosophila, too, the distribution of 

 sex-linked lethals over the X-chromosomes was found to differ 

 between X-rays and certain chemicals (11, 35). 



The discovery of specific effects of mutagens on individual 

 loci meant a great step forward in mutation research. Many cases 

 of "mutagen specificity" are now known in a variety of organisms, 

 but it is very doubtful whether all of them have a similar basis. 

 The most striking example is that of one particular region in the 

 chromosome of bacteriophage T4 (39), where mutations induced 

 by 5-bromouracil or 2-aminopurine are crowded together into pre- 

 ferred sites. While it is at least probable that these "hot spots" arise 

 from specific interactions between mutagen and genetic site, this is 

 not necessarily — and not even plausibly — so in many other cases of 

 mutagen specificity. In bacteria (24) and fungi (53), different loci and 

 different alleles of the same locus show different mutational reponses 

 to a variety of physical and chemical mutagens. In extreme cases, 

 a gene may be "mutagen stable", i.e., it may fail to respond to some 

 or all tested mutagens, while yet being able to mutate spontan- 

 eously (25). These "mutation spectra" can be profoundly changed 

 by introduction of an additional mutant gene into the same nu- 

 cleus (43). We do not yet know how this is brought about, but vari- 

 ous explanations can be envisaged and tested. An influence of the 

 residual genotype on the reaction between gene and mutagen is 

 the least likely one. We have come to realize that mutation is a 

 complicated process of which the reaction between mutagen and 

 gene is only one step, although it is the essential one. Interactions 

 between mutagen and cytoplasm, conditions of the cell preceding 

 and following treatment, degree and type of competition between 

 the newly mutated cell and the remaining non-mutated ones, as 



