The Chemical Basis of Heredity Determinants 335 



unknown ; an oxidative deamination of a few nitrogenous bases and/or 

 breakage of a few vital labile bonds might be postulated. 



8. Mustards. Herriott 29 studied inactivation of pneumococcal trans- 

 forming principle by di-(2-chloroethyl) sulfide (mustard gas). The 

 inactivation of the transforming principle (type specificity) of H. in- 

 fluenzae by various nitrogen mustards was studied by Zamenhof et al. 27 

 In both experiments the inactivating concentrations were as low as 

 10 ~ 5 M. For various nitrogen mustards the order of inactivating 

 power for the transforming principle seems to be the same as the order 

 of carcinostatic power of these compounds, thus suggesting a correla- 

 tion between these phenomena. 27 



Induction of Changes in the Active DNA Molecule 



The removal of less than 0.2% of the amino groups of the DNA 

 molecule coincides with a total inactivation of the transforming prin- 

 ciple. The treatment applied (deamination or depurination) is not 

 known to act specifically on jew amino groups or purines of special 

 importance; thus it appears that practically all the amino groups are 

 necessary for the activity of the transforming principle or, perhaps, 

 DNA in general. This view gained support when Watson and Crick 30 

 proposed their model of the DNA molecule. In this model all the 

 amino groups are indeed essential for maintaining the integrity of the 

 molecule through the hydrogen bonds. 



One might suspect that any change in the DNA molecule, whether 

 it affects the pattern of electrical changes (in depurination and deami- 

 nation) or not, results in a total inactivation or at least in a mutation. 

 The study of the effect of various agents on the transforming principle 

 in vitro thus far has not solved this problem because the extent of 

 changes which can be induced in vitro before total inactivation occurs 

 is rather small and because the nature of the changes is not always 

 known. 



It has been shown in special cases that a drastic change in the 

 chemical composition of the DNA molecule can be induced in vivo. 

 When the cells of E. coli were grown on a medium containing 5-bromo- 

 uracil, the highly polymerized DNA from these cells had up to half 

 of the thymine molecules replaced by 5-bromouracil. 31 * 32 ' 33 5-iodoura- 

 cil can also replace thymine in the DNA, but to a smaller extent, 

 undoubtedly because it is sterically less similar to the methyl group in 

 thymine. Neither of these groups bears any charge; neither partici- 

 pates in the H-bond structure of the Watson and Crick model. 30 This 

 substitution did not result in any demonstrable changes in the pheno- 



