V. MOLECULAR MECHANISM OF MUTATIONS 241 



a few review articles can here be mentioned, especially the volumes of 

 Radiation Biology (1954, 1955) and Supplement 1 of Radiation Research 

 (1959). The radiation can have a direct effect on the chromosome, e.g., 

 directly break it or alter one of the DNA bases, and an indirect effect, 

 since along the track of each particle a large number of ions or radicals 

 remain which can initiate a chain of chemical reactions. The number of 

 ion pairs produced in a given thickness of material, i.e., the ionization 

 density of the radiation, depends on the nature and the kinetic energy of 

 the particles, those of low energy giving the largest ionization density 

 (except for neutrons which at thermal energies do not excite electrons 

 but specifically interact with certain nuclei). The biological effect also 

 depends on the kind of cell and on the stage of its nuclear cycle at 

 which the irradiation is given (Marquardt, 1938) . For example, chromo- 

 somes are extremely sensitive to breakage in meioitic prophase (Sax, 

 1941; Glass, 1955). 



The inactivation of organisms often follows a first-order reaction 

 equation 



^ = -/3iV or N = Noe-0' = N.er-^'' 

 at 



where p is proportional to the intensity of the radiation. D is the "dose," 

 that is, the energy absorbed per gram of material ; it is usually measured 

 in roentgens (see Marinelli and Taylor, 1954) ; K often is a dose inde- 

 pendent constant describing the sensitivity of the organism. The fre- 

 quency of mutants per viable organisms often increases linearly with 

 the dose (Demerec and Sams, 1960) : 



M = aD 



Timofeeff-Ressovsky et al. (1935) interpreted these equations in temas 

 of a "target theory" which states that a single "hit" of the particle on 

 the "target," i.e., the genetic material, inactivates or mutates it. If the 

 inactivation follows a first-order equation one calls (3t = KD = n the 

 number' of lethal hits because than the survival is given by the zero- 

 order Poisson term iV/jYo = e~". Formally one obtains the same first- 

 order reaction equations if the radiation product produces some chemical 

 which can migrate from its origin to some other site in the organism or 

 even in the reaction vessel. But the meaning of the word "target" is 

 different and depends on the chemical or metabolic lifetime of the radia- 

 tion produced chemical, i.e., whether it can get to any place or is limited 

 to the closest surroundings of the track of the ionizing particle. If the 

 lifetime is long the radiation produces mutagenic chemicals whose con- 

 centration dejiends on the number of ionizations; in that case the amount 



