W. D. JACKSON 



oxygen levels but a marked effect at high oxygen levels was observed. If 

 we consider these experiments as a group we find some difficulty in using the 

 target theory as a functional hypothesis and it seems that the mechanism is 

 better explained by some process \\hich approaches target theory behaviour 

 only under certain limiting conditions. 



Further evidence for the form of the required working hypothesis is found 

 in the patterns of chromosome breakage. Kotval and Gray^ concluded that 

 about half of the breaks caused by a-particles are caused by particles which 

 do not traverse the chromatid. Camara^ and Jackson and Barber^*' have 

 demonstrated marked non-random distributions of simple breaks in chromo- 

 some arms. Frequency of breaks per unit length in different regions of the 

 chromosome may show a fifty-fold variation. Such differences seem to be 

 explained readily by assuming either that near misses are more effective in 

 certain regions, or that many more ionizations are rec^uired in some regions 

 before breakage occurs. Both these arguments suggest a cumulative indirect 

 action. The remarkable similarity between the distribution of breaks pro- 

 duced spontaneously and those produced by X-rays, is further evidence in 

 this direction. 



The distribution of breaks between cells also shows evidence of cumulative, 

 rather than direct action. On the basis of the target theory a Poissonian 

 distribution is expected. However, the analysis of Jackson and Barber^" 

 shows that the distribution of breaks after irradiation, like the distributions 

 after treatment with alkylating mutagens or after spontaneous breakage, 

 shows pronounced over-dispersion. There are marked tails of multiple 

 events, the variance increasing as some power of the mean. All the distri- 

 butions are fitted extremely well by the negative binomial distribution. 



This is strong evidence for cumulative action in irradiation. Breakage 

 appears to result from the cumulative action of a number of primary events 

 scattered in space and in time, each of which contributes by the diffusion 

 and collective action of active compounds or radicals. On this basis a 

 suitable model leading to a negative binomial distribution can be constructed 

 whereby cumulative contribution is obtained by incorporating a contagion 

 factor in the probability equation. If diffusion is restricted by, say, the 

 reduction in the mean free path, or when the mean number of events occur- 

 ring in a given space and time is small, then collective contribution becomes 

 negligible and damage occurs only in the local I'egion of each primary 

 event. Under these conditions, the contagion disappears and the model 

 function approaches the Poissonian limit of the target theory. Such an 

 hypothesis has at least the ability to explain direct and indirect action 

 depending on the conditions. 



There are two further lines of evidence pointing to indirect action. They 

 are: (7) the fact that variation in dose rate, by fractionation or intensity, has 

 no effect in the absence of oxygen, (2) the fact that the presence of oxygen 

 increases the frequency of damage after X irradiation but has no influence 

 on damage by high intensity radiation such as that by a-rays. Both these 

 effects can be explained on the basis of radio-chemical reactions known to 

 occur in water. This evidence points clearly to the presence of an inter- 

 mediate step between ionization and chromosome breakage. 



It has been shown by Giles and Beatty^\ ReacP"' and others, that in 



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