416 RADIATION TUOLOGY 



chain of reactions is the induction of lethal or viable mutation.s. Indeed, 

 the evidence indicates that with ultraviolet radiation the same photo- 

 reactivahle process affects both the bactericidal and mutagenic elTects of 

 radiation. Similarly, Anderson (19olb) has shown that in the case of one 

 mutation system the lethal and mutagenic effects of X rays may result 

 from the same indirect mechanism. Thus, although the existence of 

 indirect mechanisms necessitates a modification of the concept of lethality 

 t)y chemical change in one molecule, presumably the gene, by direct 

 ionization, it does not require abandonment of the hypothesis that the 

 final product of the indirect process may be lethal mutations. The 

 observation of exponential survival curves when E. coli are X-irradiated 

 in oxygen-saturated media indicates that first-order kinetics result, even 

 though it is known that a large proportion of the effects are indirect. 

 Thus the problem of determination of the best means to account for the 

 observed first-order kinetics still remains, and the plausibility of the 

 lethal-mutation theory is in no way impaired. 



There are a number of observations, however, which bear directly on the 

 lethal-mutation hypothesis. 



Lea et al. (1937) and Witkin (1947) have observed that the long fila- 

 mentous forms W'hich result from bacteria subjected to sublethal doses of 

 radiation react to subsequent exposure to radiation in the same manner as 

 normal cells and appear to be equally sensitive to radiation. Delaporte 

 (1949) has studied the filamentous forms of E. coli B cytologically and 

 reports them to be multinucleate. It would thus appear that the 

 mechanism of killing of such an elongated, multinucleate cell would not be 

 due to recessive lethal mutations, and, if the lethal-mutation hypothesis is 

 to be retained, it must be postulated that the induced lethal mutations 

 are dominant and can be expressed equally well in uninucleate and 

 multinucleate cells. 



Demerec and Latarjet (1946) in comparative studies of E. coli B and 

 B/r have shown that, with a given dose of ultraviolet, the rate of mutation 

 induction is the same for the two strains, whereas the bactericidal effects 

 are greatly different. A similar lack of correlation between the induction 

 of mutations and the lethal effects was observed when comparisons were 

 made with ultraviolet and X rays on strain B/r where, for a given survival 

 ratio, the number of mutations induced by X rays was significantly less 

 than the number induced by ultraviolet. 



Beckhorn (1950) and Lederberg et al. (1951) have approached this 

 question more directly by comparing the sensitivity of E. coli K12 cells, 

 known genetically to be diploid, with that of haploid cells of the same 

 strain. No systematic differences in sensitivity to ultraviolet radiation 

 were observed, and the most prominent effect of irradiation appeared to 

 be the conversion of diploid cells to the haploid condition. This haploidi- 

 zation occurs at doses smaller than those required for appreciable killing of 



