auerbach: effects of chemicals 127 



Acridities, which react with nucleic acid, have produced mutations 

 in at least one series of experiments with barley (22). One of them, 

 proflavine, is a very effective mutagen for bacteriophage (15). Pyronin, 

 which reacts with ribonucleic acid, is mutagenic for Drosophila 

 (18). Its overall effect is weak, but certain treated individuals 

 yield very high mutation frequencies. It seems that very special 

 conditions have to be fulfilled for its effective action (7, 19). 



Many purines produce mutations in micro-organisms (41, 70), 

 and mutations and chromosome breaks in plants (49). For many 

 years, no mutagenic pyrimidines were found in spite of attempts 

 to detect them. This has changed since it was discovered that it 

 is possible to force bacterial cells to take in analogues of the 

 normal pyrimidine bases by closing the normal pathway leading 

 to pyrimidine synthesis. Bacteria that are unable to synthesize 

 thymine may replace it quantitatively with offered bromouracil. 

 Mutations occur in such bacteria and in bacteriophages grown on 

 them (13, 57, 79). 



The fact that bromouracil is so readily incorporated into 

 bacterial DNA makes it tempting to assume that it is mutagenic 

 through incorporation, and ingenious schemes of mutagenesis 

 through base changes in the genetic DNA have been based on this 

 assumption (40). Some mutagenic purines, such as caffeine, are 

 either not incorporated at all or only in indetectably small amounts 

 (69) and proflavine probably does not act by incorporation. For 

 purines, interference with enzymes concerned with nucleic acid 

 metabolism has been suggested as an alternative cause of muta- 

 genic ability (69). Particularly interesting, though still unexplained, 

 is the fact that in bacteria mutagenesis by purines like caffeine and 

 theophylline can be prevented by "antimutagens" in particular 

 adenosine riboside (69). Radiation-induced mutation frequency is 

 not depressed by these antimutagens, and a certain proportion of 

 spontaneous mutations is likewise refractory to them. A search for 

 similar systems of mutagen-antimutagen balance seems a promis- 

 ing approach to a study of the complex biochemical interactions in 



mutagenesis. 



Nitrous Acid 



In 1939, Thorn and Steinberg (90) produced variants in Asper- 

 gillus grown on food with an admixture of mannitol-nitrite. Ten 



