SYLLABUS 111 



five cofactor molecules. At low cofactor concentrations, when only a 

 small fraction of the key places have the necessary five cofactor mole- 

 cules, the number of key places gaining activity per unit time will 

 vary with the fifth power of the cofactor concentration. At high co- 

 factor concentrations, when all key places have at least five cofactor 

 molecules within them, the rate of activation will be independent of 

 the cofactor concentration. Deactivation is thought to occur when one 

 of the five cofactor molecules from an active key place breaks loose. It 

 is, however, possible for another, exogenous cofactor molecule to take 

 the place of the lost one if it can react in time with the remaining four 

 molecules of a recently deactivated key place. Thus, the efficiency of 

 low cofactor concentrations in retarding deactivation depends on the 

 first power and not, as is true in the case of activation, on the fifth 

 power of the cofactor concentration. 



The efficiency of a given low cofactor concentration in activating 

 the phage is drastically reduced by lowering the temperature. This is 

 readily understood in terms of the above model. If the probability of 

 finding a cofactor molecule within a key place at a given cofactor con- 

 centration is slightly less at a lower temperature, say, because of a 

 weak bond being formed less readily, then this reduction makes itself 

 felt to the fifth power in the observed activation rate. 



11. Radiation Inactivation. A phage particle is defined as inactive 

 when it is not able to give rise to phage growth; ordinarily this ability 

 is tested by plaque formation. The inactivating influence of radiation 

 is studied by determining survival curves, i.e. curves obtained by plot- 

 ting the logarithm of the fraction of particles active after a dose D of 

 radiation. Frequently this curve is a straight line indicating that the 

 inactivation is the result of a single event ("hit"). In these cases, a 

 dose which gives a survival of e'^ (0.367) is called the "inactivation 

 dose" with the negative of the natural logarithm of the surviving frac- 

 tion giving the average number of hits per particle. 



(a) Inactivation by X-rays. Two types of inactivation. By direct 

 and by indirect effect (Luria and Exner, 1941; Watson, 1950). 



(1) Inactivation by Direct Effect. This refers to inactivation due 

 to absorption of energy within the phage particle. It is obtained 

 when phage is suspended during irradiation in a protective medium 

 (broth, gelatin solution, tryptophane solution, etc.). The survival 

 curve is perfectly straight indicating a one hit inactivating me- 

 chanism. The rate of inactivation is dependent on dose only. It is 

 independent of intensity, fractionation of dose, the presence of 

 oxygen, and the temperature during irradiation. The quantum 



