Nucleic Acids and Nucleoproteins 67 



Let us turn now to the so-called radiomimetic agents 

 like the nitrogen mustards, which are capable of producing 

 (1) chromosome breaks, and (2) mutations. In vitro they com- 

 bine with DNA in various ways, especially with — NHg and 

 — OH. Combination with phosphate groups may also occur 

 but will in general be rather labile. The effect of combination 

 with the — NH2 and — OH groups is to break up the hydrogen- 

 bonded structure of DNA, which has been shown to be fol- 

 lowed by a slow degenerative breakage of nucleotide chains, 

 probably caused by hydrolysis of triply esterified phosphate (see 

 Butler, Gilbert and James, 1952). It might be asked if this 

 kind of reaction actually occurs in vivo, especially since there 

 are so many competing molecules such as proteins with which 

 reaction could occur. 



It has been found that (1) when a nitrogen mustard (in this 

 case a radioactively labelled phenylalanine nitrogen mustard) 

 reacts with intact deoxyribonucleoprotein in aqueous medium, 

 reaction occurs with both the DNA part and the histone part 

 in the ratio of about 2 : 1 (Table I). This means that nitrogen 



Table I 



Reaction of a Nitrogen Mustard p-Di(2-Chloroethyl)amino-dl-i*C- 

 Phenylalanine with Deoxyribonucleoprotein Extracted from Various 



Tissues. 



(Experiments by J. A. V. Butler and A. R. Crathorn.) 



Activity in Activity in 



DNA Fraction Protein 



Calf Thymus (dried preparation) 3-24 1-03 



Rat Thymus (fresh wet preparation) 4-27 2-09 



Spleen preparation 2-62 2-20 



mustards can easily react with DNA even when the latter are 

 combined with histone; (2) when the same nitrogen mustard is 

 introduced into the rat, within a period of 1-3 hours (and 

 possibly shorter times) reaction has occurred with DNA and 

 RNA in all the cell fractions and in all the organs examined 

 (Table II). These substances therefore react very extensively 

 with nucleic acids in vivo. 



