k.\i)I()hi(M.()(;ic:ai. mi'.chanism ai' riii: ciJ.i.ri.AR i.ia'EL 



of irradiation in a nicdiuni containiiii; If) ixM/l. of dissolved oxygen, is 

 consuinod radiochriiiically after the eell has been exposed to a dose of around 

 3, out) U) '),()0() rad. Tlie concentration of oxygen within tlie bacillus is 

 unknown, but assuming it to be comparable with that outside the cell, the 

 total organic peroxide formation may well amount to 15 ji,M/l. — or higher in 

 the case of cells exposed to larger doses under conditions of continuous 

 aeration. Although some organic peroxides are known to be mutagenic, and 

 particular peroxides such as cumene hydroperoxide and disuccinoyl mono- 

 peroxide are biologically active towards micro-organisms, viruses, and 

 transforming principle at extremely low concentrations^", attempts to 

 implicate peroxides in particular types of biological damage induced by 

 ionizing radiation have generally been inconclusive or negative-". This is 

 probably because most cells are adecjuately protected by their catalase 

 content. In an interesting investigation with a haemin-deficient strain of 

 Escherichia coli, recently reported by Adler and Stapleton-^ it has been 

 shown that, in the absence of catalase, E. coli exhibited a progressive loss of 

 colony-forming ability after irradiation, which closely resembles the 'after 

 effect' of radiation originally reported by Alper'--. In this case, the total effect 

 on the irradiated aerobic cell appears as a sum of three components, viz- («) 

 damage which is independent of peroxide formation, (b) damage which is 

 dependent on the absorption of oxygen but not on the effects of peroxides 

 acting after the end of irradiation, and (c) on an 'after effect' which can be 

 simulated by the treatment of the irradiated (but not the unirradiated) cell 

 by chemical hydrogen peroxide or hydrogen peroxide resulting from the 

 exposure of the medium to the given dose level. 



At the outset of this Conference Sir Macfarlane Burnet enunciated four 

 questions concerned with genetic damage and carcinogenesis, to which he 

 hoped answers would be forthcoming. Two of these questions were : ' Can 

 what is determined of the genetic effects of radiation in the laboratory be 

 pushed down to the very small levels found in Nature ? ' and ' How does the 

 effect of ionizing radiation vary with its strength ? ' 



We find ourselves in a dilemma because any conceivable experiment which 

 we might set up to obtain answers to these questions, by use of laboratory 

 animals, still leaves a very large gap in dose rate and over-all time of irradia- 

 tion to be bridged by extrapolation, and we have no theory of radiobiological 

 damage so well founded that it can be used with complete confidence to 

 bridge that gap. While acknowledging that we cannot at present answer 

 Sir Macfarlane's questions, it is perhaps worth noting that there are certain 

 circumstances in which it is possible to extrapolate with confidence to as low 

 a dose or as low a dose rate as we please on the basis not of a theory, but of 

 a physical fact, namely that ionizing particles deliver their energy to matter 

 in quanta of considerable magnitude. It follows (r/. Paper 1) that for a cell 

 (or element of tissue) of any size, there is a dose Dg which we may call a 

 single particle dose, and which has the following significance. If a large 

 number of such cells or elements of tissue are exposed to this dose, an average 

 of one particle will cross each volume element. The actual numbers will be 

 distributed in accordance with the Poisson formula, so that about one-third 

 will not be traversed by any ionizing particles at all, about one-third would 

 be traversed by a single particle, one-sixth would be traversed by two parti- 



286 



