INACTIVATION OF VIRUSES 1569 



1956). Two compounds were used, cumene hydroperoxide and succinic per- 

 acid, which both inactivated the coliphages of the T series and phage A 

 (active on strain K12 of £". coli). Different resistance patterns were observed 

 for peroxides and for X-rays, the small phages (Tl, T3, and T7) being the 

 most sensitive to peroxides but the most resistant to X-rays. The chemical 

 complexity encountered in this field is borne out: (1) by the observation tliat, 

 of the two peroxides tested, only succinic peracid inactivates free DNA 

 (transforming principle); (2) by the occurrence of unpredictable interactions 

 between the peroxide added and slight impurities in the phage preparations. 



A striking feature of inactivation by reducing radicals was discovered by 

 Alper (1952a,b) and termed "part-inactivation." After moderate X-ray irrad- 

 iation, survivors of phage T3 or SI 3 show greatly increased sensitivity to the 

 toxic components in preirradiated buffer: they have become sensitized, so to 

 say. With SI 3, the ratio of sensitized to fully inactivated particles changed 

 from 10 : 1 to 1 : 30 when increasing the dose from 1000 to 20,000 rad., and it 

 could be shown that the fraction of particles not inactivated and not sensitized 

 decreased exponentially (Alper, 1955). If this is taken to mean that a single 

 event is sufficient to sensitize, inactivation, via sensitization, must be at 

 least a two-step reaction. It has recently been foimd that X-rays sensitize 

 phage T4 to inactivation by ascorbic acid; this radiation effect is mimicked 

 by cumene hydroperoxide but not by succinic peracid (MaxweU, quoted by 

 Latarjet, 1956). 



The direct effect of X-rays is, by definition, the effect remaining when the 

 indirect action has been effectively eliminated. Two main criteria have been 

 used to evaluate how weU this has been achieved: (1) that maximum protec- 

 tion has been reached; and (2) that inactivation is independent of dose rate 

 (in Roentgens/min.). 



The experiments of Luria and Exner (1941a, b) and Watson (1950) showed 

 that, above a certain broth or peptone concentration, the rate of inactivation 

 remained virtually constant, and it was concluded that all indirect effects 

 had been eliminated. It is certainly true that most of the indirect effect can 

 be eliminated in this way, but, as mentioned above, it is possible that a less 

 significant class of indirect effects remains, which camiot be shielded against 

 m solution (Latarjet and Fredericq, 1955; Bachofer et al., 1953). 



The principle of dose-rate independency will be obeyed if nothing but direct, 

 immediate, and irreversible inactivation occurs (Jordan, 1940; Lea, 1947). 

 That it camiot be expected to apj)ly to indirect effects is easy to see when 

 considering that the concentration of radicals and toxic compounds attained 

 during X-ray irradiation depends strongly on dose rate (Bonet-Maury and 

 Lefort, 1950). Dose-rate mdependence was demonstrated in the phage ex- 

 periments of WoUman et al. (1940) and in experiments with dry preparations of 

 vaccinia virus and some phages carried out by Lea and co-workers (Lea, 1947). 



