10 p. ALEXANDER AND Z. M. BACQ 



way, and it only blocked 30 per cent of the total SH groups of the cell. 

 Treatments that lead to the loss of more SH groups were toxic. It is 

 not surprising that the extent of sensitization was so small under these 

 conditions. Pre-treatment of bacteria with SH reactors leads to very 

 much greater sensitization. Exposure to 10"4 M iodoacetamide doubles 

 the radiosensitivity oi Pseudomoyias flnorescens and it increases that of 

 Micrococcus soclensis seven times. Post -irradiation exposure to iodo- 

 acetamide is without effect on the survivors. These very great changes 

 in radiosensitivity may not be due solely to the removal of protective 

 SH-compounds but may be due to a change in the physiological state 

 of the cell due to the blocking of SH-enzymes (Alexander and Mikulski, 

 1961). 



IS THERE A MOLECULE OR A SERIES OF MOLECULES WHICH MAY 

 BE FOUND ALTERED IMMEDIATELY AFTER IRRADIATION IN VI VO 

 WITH DOSES GIVING IMPORTANT ANATOMICAL LESIONS AFTER A 



LONG LATENCY? 



All organic molecules are susceptible to damage by radiation and 

 in the irradiated cell almost every constituent is liable to be altered 

 chemically by the direct or indirect action of radiation. A consequence 

 of this almost complete absence of selectivity is that a high proportion 

 of the few reactions that occur will be harmless as they do not involve 

 a molecule (or structure) of which nearly every one is essential to the 

 cell. 



Two kinds of molecules — enzymes and nucleoproteins — are at first 

 sight possible candidates for the essential lesion. 



Eyizymes 



When purified enzymes are irradiated in vitro — with large doses — 

 a decreased activity is regularly observed, f When enzymatic activities 

 are tested very soon after moderate irradiation in homogenates, tissue 

 slices or whole organisms inhibition — even slight inhibition — (cf. DNA 

 and protein synthesis in cells irradiated in tissue culture is rarely 

 noted. On the contrary, anabolic as well as catabolic enzymatic actions 

 are generally found increased, sometimes as much as ten times (for 



t The chemical mechanism by which ionizing radiations inactivate enz^aiies deiiends 

 on whether the action is direct or indirect. If direct, a single primary ionization is often 

 sufficient to disorganize the whole of the secondary structure of a protein by causing the 

 breakage of liydrogen bonds (Alexander ct al., 1959). The radicals from water (i.e. in- 

 direct action) react chemically with the protein, but the majority of the reactions occur 

 on groups that are not essential for biological activity and these reactions do not lead 

 to inactivation. Only occasionally (ranging on average from one in ten to one in one 

 hvmdred) does a radical inactivate by reacting with an essential site. Consequently, naany 

 ionizations have to occur in water before a protein is inactivated by "indirect action" 

 and this therefore is much less efficient than direct action. 



