Pyrimidine Aioieties in Animals, Plants, and Bacteria 81 



induced mutations have been suggested on the basis of this con- 

 cept. Watson and Crick (77) pointed out that the specificity in 

 DNA structure (adenine pairing with thymine and guanine with 

 cytosine) resuhs from the assumption that each of the bases 

 possesses one tautomeric form which is very much more stable 

 than any of the otlier possibilities. The fact that the compound is 

 tautomeric, however, means that the hydrogen atoms can occasion- 

 ally change their location. Thus, a spontaneous mutation might 

 be caused by a base occurring very occasionally in one of the less 

 likely tautomeric forms at the moment when tlie complementary 

 chain is being formed. For example, whereas adenine will nor- 

 mally pair with thymine, if there is a tautomeric shift of one of 

 its hydrogen atoms, it can pair with cytosine. The next time 

 pairing occurs, the adenine (having resumed its more usual 

 tautomeric form) will pair with thymine, but the cytosine will 

 pair with guanine, and so a change in the sequence of bases will 

 have occurred. 



Mutations may also be induced by chemical agents. Let us 

 consider two categories of chemically induced mutations: 1) those 

 which result from the conversion of one nucleotide base in a 

 DNA chain co another nucleotide base (transition), and 2) those 

 which result from the deletion of a base from the chain. 



The conversion of cytosine to thymine may be effected by 

 adding nitrous acid to cells (58). Cytosine is deaminated by 

 nitrous acid to uracil. When DNA which has been deaminated 

 in this way undergoes replication, the uracil will attract adenine 

 during the complementary base pairing. The next time pairing 

 occurs (second cycle of replication) the adenine which had paired 

 with uracil will now pair with thymine. Hence, following two 

 cycles of DNA replication, the original cytosine-guanine base pair 

 will have been converted to a thymine-adenine base pair. 



A mutagenic change from thymine to cytosine may be induced 

 in cells by the use of the thymidine analog, bromodeoxyuridine (21). 



A nucleotide base change in the DNA chain expresses itself 

 as an amino acid change in the protein chain whose synthesis is 

 controlled by the altered DNA. 



A third mutagenic agent, nitrogen mustard, may alkylate some 

 of the guanine groups of the DNA chain at the N(7; position. 



