V. MOLECULAR MECHANISM OF MUTATIONS 



237 



with DMS mainly produces 7-methyIguaninc (Reiner and Zamenhof, 

 1957). In addition 1-niethyladenine, some 3-mcthyIadenine and 1,3- 

 dimethyladenine, and some cytosine derivative are formed (Brookes and 

 Lawley, 1960a). Ethylation of the bases is less effective but some 

 7-ethylguanine has been found after treatment of DNA with DES 

 (Bautz and Freese, 1960). The preferential formation of 7-alkylguanine 

 has also been found for nitrogen mustard (Brookes and Lawley, 1960b). 

 Lett et al. (1962) argue that the alkylation of the base does not 

 occur directly but by transalkylation, the alkyl group changing from the 

 phosphate to the base; for our purposes it is unimportant by which 

 mechanisms the bases are alkylated. The alkylated base might in- 

 hibit DNA duplication or cause base pairing mistakes during DNA 

 duplication. 



4. Depurination. The alkylation of purines in the 7-position (see 

 Fig. 14) gives rise to quaternary nitrogens which are unstable. Either 



CH, 



I 



CH, 



I 



O 



N N NH, 



I ' 



R 



m 



IV 



NH 



NH, 



NH, 



+ROH 

 +H+ 



Fig. 14. Guanine removal by ethylation. I and II: Mesomeric states of 7-ethyl- 

 deoxyguanosiue. Ill: Liberation of the ethyl-group. IV. Decay into 7-ethylguanine 

 and deoxyribose. 



the alkyl group itself hydrolyzes away from the purine or else the 

 alkylated purine separates from the deoxyribose leaving it "depuri- 

 nated." The liberation of ethylated and methylated purines from DNA 



