240 ERNST FREESE 



DXA, either (luring growth or before, when the treated DNA is incubated 

 at elevated temperatures. Nevertheless, the alkylation of A seems to 

 have some although a smaller mutagenic effect as will be seen in Section 

 V,B,4. 



It is interesting to note that the methylating agents also have some 

 mutagenic effect: DMS is able to induce the reversion of certain Xeuro- 

 spora mutants (Westergaard, 1957) and MMS induces the reversion of 

 certain bacterial mutants (Strauss, 1962). The frequency of these muta- 

 tions could not be increased by incubation subsequent to treatment 

 (Strauss, 1962) ; they may have been induced by another one of the five 

 mechanisms mentioned or by an indirect effect. 



The emphasis on the explanation of point mutations should not distract from 

 the fact that alkylating agents can also induce large alterations. For example, 

 Xasrat et al. (1954) have shown in Drosophila that mustard gas induces trans- 

 locations whose frequency increases with the square of the frequency of lethals: 

 these alterations presumably are caused by a break in each of the two 

 cliromosomes involved. 



Formaldehyde may also be classified as an alkylating agent. It can 

 react with proteins (Putnam, 1953), with RXA (Fraenkel-Conrat. 1954), 

 and with single- but not with double-stranded DNA (Staehlin. 1958). 

 It forms monomethylol groups ( — NH — CH...OH) with the amino groups 

 of the non-hydrogen-bonded nucleic acid bases; these bonds can either 

 slowly break again or the hydroxymethyl group can react with some 

 other group to form methylene bridges (Staehlin, 1958). Even native 

 DNA can apparently react to some extent with fomialdehyde, at least 

 in its native state inside a phage, since Sauerbier (1960) has shown, by 

 experiments with multiplicity reactivation, that the inactivation of 

 phage Tl by formaldehyde is not caused by an efTect on the injection 

 mechanism. The mutagenic mechanism of fomialdehyde (Rapoport, 

 1946; Auerbach and Moser, 1953) is not yet understood. Formaldehyde, 

 if UV-irradiated shortly before use for mutagenic treatment, is more 

 nmtagenic (Jensen et al., 1951) ; peroxides also increase its mutagenicity 

 (Dickey et al, 1949; Sobels, 1956). This suggests that either a radical 

 or a peroxide is the active mutagenic agent of formaldehyde, unless the 

 combined action of the two agents produces an additional mutagenic 

 effect. 



E. RADIATIONS 



1. Ionizing Radiations 



The biological effects of X-rays and y-rays, a particles, protons, high 

 energy neutrons, and electrons have been studied so extensively that only 



