Ill DNAandgrowth — MITOSIS 271 



{e) Effects of physical and chemical agents on DNA and its synthesis 



Fvirther evidence, although of a more indirect nature, for the important role 

 of DNA in genetics and cell division can be found in many studies on the effects of 

 various agents on mutational rate and mitotic activities : all of them have been 

 found to act on DNA or its synthesis. 



Of greatest interest in this respect is probably ultraviolet (U.V.) radiation as it 

 has been shown that the action spectrum of U.V. radiation in inducing mutations 

 in various organisms {i.e. its effectiveness at various wavelengths) is similar to the 

 absorption spectrum of nucleic acids (Hollaender and Emmons, 1941 ; Stadler and 

 Weber, 1942). It should be pointed out, however, that the absorption spectra of 

 DNA and RNA are almost identical; but since the mutations studied were truly 

 chromosomal, and since DNA is usually present in much larger amounts than 

 RNA in chromosomes, there seems to be little reason left to doubt that the U.V., 

 in these experiments, was really acting on DNA. Furthermore, it has been clearly 

 shown by several workers (especially Hollaender et al., 1941, and Errera, 1952) 

 that prolonged U.V. irradiation modifies the physical properties of DNA, prob- 

 ably by producing some kind of depolymerization. 



However, DNA itself is less sensitive to U.V. radiations than DNA synthesis: 

 as found by Kelner (1953) and by Kanazir and Errera (1954), low doses of U.V. 

 are enough to inhibit DNA synthesis in E. coli; RNA and protein synthesis still 

 go on in the irradiated bacteria, although cell divisions are completely inhibited. 

 Thus, in this case, growth proceeds at an almost normal rate in the absence of 

 nuclear division. The result is the formation of filamentous bacteria containing 

 only a few nuclei (Errera, 1 954) . Other instances, where DNA synthesis can be disso- 

 ciated from growth, RNA and protein synthesis, will be examined in section iv, p. 275. 



A similar situation is found in the case of other well-known mutagenic agents, 

 the mustards : sulfur mustard was the first chemical substance found to be capable 

 of inducing mutations in Drosophila (Auerbach and Robson, 1946); according to 

 Herriott (1948), sulfur mustard is much more active on DNA than on protein or 

 RNA. In the case of nitrogen mustard, as of U.V. , DNA depolymerization occurs 

 at relatively high concentration (Butler et al., 1950), while DNA synthesis is much 

 more sensitive than RNA synthesis : this has been found to be the case both with 

 amphibian eggs (Bodenstein and Kondritzer, 1948) and bacteria (Herriott, 1951b). 



Another interesting case is presented by the methylated purines, caffeine and 

 theophylline, which are mutagenic for bacteria, and it is remarkable that their 

 effect is counteracted by nucleosides of the normal bases (Novick and Szilard, 

 1952). These results might well mean that the methylated purines are incorpo- 

 rated in the nucleic acids instead of the normal purines : this would lead to the 

 synthesis of abnormal nucleic acids which, in turn, might be at the origin of the 

 observed mutations. However, such a simple explanation appears to be of doubtful 

 value, since Zamenhof and Griboff ( 1 954) have found that incorporation of 1 7- 1 9% 

 of the abnormal base 5-bromouracil in the DNA of E. coli has no effect on the 

 growth rate; nor does it lead to mass-mutations. 



However the possibility of a slight or moderate mutagenic effect of 5-bromo- 

 uracil is not ruled out by Zamenhof and GribofT's (1954) experiments; furthermore, 

 we do not know yet whether the incorporation of the abnormal base occurs in all 



Literature p. 2gr) 



