DAMAGE IN AEROBIC AND ANAEROBIC SYSTEMS 43 



tumerman: I would like to i^oint out the possibility that the important role of 

 the water in radiobiological effects is due not only to the formation of the i-adio- 

 lysis i^roducts, but also to the fact that water has a structure, damage to which 

 may contribute to the formation of the long lived triplet states. 



passynsky: Probably with the aid of the micro-impulse technique Dr. Gray 

 used it would be possible to determine the minimum time for the interaction of 

 oxygen Math the irradiated substance, which ought to depend on oxygen pressure. 



ALEXANDER : I caniiot agree with Dr. Gray that dose-response curves can be used 

 to give quantitative information concerning the nature of the initial lesion in 

 cells. There is now abundant evidence that every type of radiation lesion is 

 capable of restoration after irradiation and that the magnitude of this restora- 

 tion can be altered experimentally. Even if no special steps are taken to effect 

 restoration, some is always taking jolace following irradiation. Moreover, it seems 

 highly probable that radiation is also affecting the repair mechanism and this 

 cannot therefore be assumed to introduce a constant factor which merely affects 

 the size of the target calculated. The probability that ionization will produce a 

 l^articular lesion is thus not governed only by "target size" considerations, but by 

 a whole host of post-irradiation metabolic factors quite apart from protection 

 and energy transfer phenomena which smear out the size of the target. In this 

 complex chain of events, there would seem to be no direct or constant relation- 

 ship between the end-effect and the initial act of ionization such as is necessary 

 for the interpretation of dose-response curves along the lines you indicated. 



The interpretation of the general shajae of the curve in terms of multiplicity 

 of events also seems to be unjustified since the effect of irradiation on the effect- 

 iveness of repair may well cause a curve to steepen progressively or to make an 

 otherwise hyperbolic curve appear linear. I believe that it is quite likely that 

 exponential dose-response curves of the type you showed for bacteria are the 

 consequence of several factors acting in conjunction. This view derives support 

 from the important work of Hollaender in which he showed that the shape of the 

 dose-response curve of bacteria could be altered drastically by small changes in 

 experimental conditions. 



gray: I cannot understand why the fact that different dose-response relations 

 are observed under different metabolic conditions should be a ground for reject- 

 ing an interpretation of each of these dose-response relations in terms of the 

 nmnber and probability of the initiating events which are radiobiologically 

 significant vmder the respective metabolic conditions. 



In my view the dependence of dose-response relations on metabolism is, in 

 part, a natural consequence of the facts mentioned in the earlier part of Dr. 

 Alexander's remarks, namely that many of the injuries sustained by cell com- 

 ponents are repairable under certain metabolic conditions, but not under others. 

 In part, it is probably a reflection of the fact that the significance, for the chosen 

 criterion of biological damage, of an injury sustained by a particular organelle 

 will depend on what metabolic activities the cell has to engage in after iiTadiation 

 e.g. whether or not it has to adapt to a set of culture conditions different from 

 those under which it was grown previously to irradiation. Propei'ly used, the 

 dose-response relation can be a valuable guide to the investigation of the mech- 

 anisms which underly the modification of biological response by post-ii'radiation 

 metabolism. 



By a dose-response relation I mean a curve, or its mathematical expression, 



