MUTATION AS A CHEMICAL PROCESS 221 



turns out that the target is always considerably smaller than the whole 

 cell, and would seem, therefore, to be some cell particle, perhaps the 

 gene. A number of other quantitative observations fit the target theory; 

 for example, the absence of an observable threshold of dose, indepen- 

 dence of the wave length and intensity of the radiation employed, and a 

 cumulative effect even when doses are intermittent. The theory contains 

 assumptions, however, which have not been subjected to a sufficient 

 number of independent tests to warrant unreserved confidence. Further- 

 more, there is evidence that X-rays may, in part, act indirectly. 



Some mutations are lethal and prevent the cell from growing in a 

 given environment. A mutation lethal in one environment may be viable 

 in another. For example, a mutation inducing a requirement for leucine 

 is lethal when that amino acid is absent, but viable when it is present. 

 Other lethals are caused by defects which cannot be repaired, perhaps, 

 in some cases because they concern the synthesis of essential and non- 

 diffusible protein molecules. Then again, many cells may be killed by 

 radiation because of the inactivation of cell structures other than 

 chromosomal genes. If one or another of these processes were responsi- 

 ble for most of the cell deaths resulting from irradiation, then its 

 response to dose could be measured. Often, after exposure to different 

 doses of X-rays, one-hit killing curves are obtained, as in the case with 

 the induction of mutants. But because it is not possible to measure small 

 numbers of dead cells among large numbers of survivors, heavy doses 

 must be employed and the number of survivors decreases significantly 

 with each unit of dose. Nonetheless, if each unit of dose kills the same 

 fraction of survivors, then, when the log of the fraction surviving is 

 plotted against dose, a linear killing curve is obtained. An example is 

 shown in Figure 8.11, which follows the relation: 



S = ^=e-'"' (8.4) 



No 



where S is the fraction surviving, e is the constant 2.718, N is the number 

 surviving after dose D, Nq is the initial number, and k is a measure of 

 the sensitivity of the cellular unit being inactivated. When two or more 

 units need be inactivated for death to occur, the survival of either one 

 resulting in viability of the cell, another relation, also shown in Figure 

 8.11, is obtained. It follows the equation: 



S = I - {I - e-'^'^r (8.5) 



where n is the number of units. Upon the application of low doses, most 

 cells still have at least one surviving unit, but with larger doses even 

 these become inactivated. Eventually, the only cells surviving are those 



