272 RADIATION BIOLOGY 



INDIRECT AND DIRECT ACTION THEORY 



As already mentioned, the indirect action theory supplements the 

 direct action or target theory. The indirect action theory conceives the 

 whole solution as the target (Dale, Meredith, and Tweedie, 1943), whereas 

 the direct action theory, in its narrowest sense, confines the target to a 

 particular molecule in which the primary event, i.e., an ionization, has to 

 occur, or through which or near which an ionizing particle has to pass. 

 While there is no doubt that both modes of action of radiation are valid, 

 the indirect action theory is more flexible with regard to the proximity of 

 the primary event to the molecule affected. Further, unlike the target 

 theory, it does not need to postulate unit ionic yield, i.e., one molecule 

 changed per ionization, to explain the exponential curve. In fact, ionic 

 yields exceeding unity can occur in the dry state of matter as well as in 

 solution. The size of the biological molecule appears to have no relation- 

 ship to the ionic yield. Viruses have an ionic yield of 1, and the much 

 smaller molecules of carboxypeptidase in a 15 per cent aqueous suspen- 

 sion, being a semisolid column of crystals, still have the same ionic yield 

 of 0.18 as in a 0.1 per cent solution. On the other hand, still smaller mol- 

 ecules, e.g., amino acids, both in solution and dry, can react with an ionic 

 yield exceeding unity. 



The difference, it may be argued, between the two modes of action — 

 direct or indirect — will be the more irrelevant the nearer the origin of 

 active radicals lies to the molecule or structure upon which they act. 

 According to this view the two theories would merge at some point. The 

 distance over which the indirect action can operate (Allsopp, 1948; 

 Moelwyn-Hughes, 1947) can be left undecided until more information 

 comes to hand. 



On the other hand it will be well to keep in mind that the actual mech- 

 anism, whether it is ionization or reaction with radicals, can have an 

 important bearing on the explanation of the biological effect. Radiation- 

 induced breakage of chromosomes, for instance, is a biological effect 

 observed. Merely to suggest ionization as the cause does not lead beyond 

 the fact of breakage. The picture of an ionizing particle, traversing a 

 chromosome and leaving in its track a break, is an inducement to taking 

 it for granted that a break occurs just at that point where the particle 

 crosses. This is not necessarily so. The break could be the result of 

 release of stresses in long-chain molecules triggered off by a reaction with 

 radicals somewhere else. To consider the mechanism in terms of a chem- 

 ical reaction between radicals and constituents of chromosomes may 

 yield information on the chemical architecture of the chromosomes them- 

 selves. Progress in this direction together with, information obtained 

 from the action of other chemical agents, e.g., the nitrogen mustards, 

 which also cause breakage of chromosomes could be of great value. 



