V. MOLECULAR MECHANISM OF MUTATIONS 245 



tcrial division following UV treatment (Witkin, 1956; Haas and Doud- 

 ney, 1957). 



The effect of UV has also been studied in other organisms; both 

 mutations and chromosomal aberrations have been observed (e.g., Swan- 

 son and Stadler, 1955; Kirby-Smith and Craig, 1955; Pomper and 

 Atwood, 1955). In yeast a mutagenic spectrum of UV-induced point 

 mutations has been detennined (Leuppold, 1962). 



UV-irradiation of the pyrimidines produces unstable base analogs. 

 The major effect is apparently the saturation of the double bond 

 between the 5- and 6-position by water. (For a review see Shugar, 

 1960.) The reaction product of cytosine readily reverts at neutral pH 

 when the irradiation is shut off. Nevertheless, this product or some 

 derivative may be the cause of mutations. The reaction product with 

 thymine is more stable and reverts quickly only on heating or 

 acidification. 



Recently Beukers and Berends (1960) have shown that UV-irradia- 

 tion of concentrated thymine solutions as well as of DNA jiroduces a 

 thymine dimer. The reaction apparently goes via a higher energetic 

 triplet state. This dimer has also been found in the DNA of UV- 

 irradiated bacteria (Wackcr et al., 1960b). One can readily understand 

 the lethal effect of the dimer formed in DNA since DNA replication is 

 probably stopped at this place; but it is an open question whether the 

 dimer has anything to do with UV-induced mutations. 



F. UNCLASSIFIED MUTAGENS 



Certain mutagens are hard to classify since so little is known about 

 their chemical site of mutagenic attack. Such agents are, for example, 

 manganese chloride (Demerec and Hanson, 1951), whose effect depends 

 on the pretreatment of the bacteria, and several heavy metals (Glaess, 

 1956) and alkaloids (Ochlkcrs, 1949) in higher organisms. Another agent 

 is 4-nitroquinoline-l-A^-oxide, which is mutagenic for tobacco mosaic 

 virus RNA (Endo et al., 1961) and for bacteria (Mashima and Jkeda, 

 1958) but it is not clear whether its mutagenicity is due to the liberation 

 of nitrous oxide or to some other effect. Also DoO was found to induce 

 mutations slightly in bacteria (De Giovanni, 1960, 1961) and phages 

 (Konrad, 1960) grown in its presence. 



G. SPONTANEOUS MUTATIONS 



The only reasonable operational definition of "spontaneous" muta- 

 tions is that these are mutations produced under "normal" growth 

 conditions. Both the frequency and specificity of these mutations may 

 therefore depend on the growth medium, temperature, pH, etc., which 



