DAMAGE TO KEPKODUCTIVE CAPACITY OF HUMAN CELLS 187 



survival curve is obtained up to at least 400 rad (Fig. 1, curve 1'). The 

 mean lethal dose (LD37) is found to be 65 rad. 



The ex])onential survival curve may be represented by 



= e-.SD 



n 



"0 



in which uq is the number of cells plated, li is the numlier of cells sur- 

 viving a dose of a-radiation D and *S' is a constant, which may be inter- 

 preted as a "sensitive area" if Z) is expressed in a-particles per unit area 

 passing through the cells. Taking an average LET of 170 keV//x for 

 a-particles of 3-4 MeV, one a-particle passing per square micron is 

 equivalent to an average dose of ;2,720 rad. From the LD37 of 65 rad S 

 can be calculated to be 42/^^, which corresponds to a circular area of 

 7-4jLt diameter. This very large sensitive area is about equal to the area 

 presented to the a-radiation by the nuclei of the cells, which, by 

 microscopic examination, were found to range between 6 and 10/t in 

 diameter. As it is generally accepted that the nucleus of a cell is much 

 more sensitive to ionizing radiation than the cytoplasm, it seems very 

 unlikely that any structure in the cytoplasm can be correlated with this 

 sensitive area of about 42^2 Thus the cross-section of the nucleus must 

 be identical with the sensitive area calculated from the experiments. 

 This suggests that whenever one a-particle penetrates the nucleus any- 

 where, the cell is sufficiently damaged to become incapable of un- 

 limited proliferation. 



The survival curves obtained with /8- and X-radiation are not expo- 

 nential but the slope of the tangent increases with increasing dose. For 

 the curve obtained with 200 kV X-radiation this slope corresponds at 100 

 rad to a mean lethal dose (LD37) of about 400 rad, at 700 rad to an LD37 

 of about 180 rad and at 1,300 rad to an LD37 of about 100 rad. It may be 

 noted that as a result of this difference in shaj^e between the survival 

 curves the relative biological efficiency (RBE) of a-radiation, defined 

 as the ratio of doses of 200 kV X-radiation and a-radiation which cause 

 the same effect, ranges from 2-5 at 0-017 per cent survival to at least 6 

 at 80 per cent survival. The survival curve obtained with /8-radiation 

 has, up to doses of 900 rad, a shape which is not significantly different 

 from the curve obtained with 200 kV X-radiation (Fig. 1, curve 2). From 

 the results the RBE is calculated to be 0-85 ± 0-10. The same con- 

 clusion may be drawn from curve 4 obtained with 20 kV X-radiation, 

 for which the RBE is calculated to be 1 -15 ± 0-10. 



The shape of the 200 kV X-ray survival curve suggests that some 

 sort of accumulation of damage takes place. Puck (1959) assumes for 

 the explanation of a similar curve obtained with 150 kV X-radiation a 



