40 L. H. GRAY 



The influence of mefabolism on the aerobic and anaerobic sensitivities of 

 cells, ivith special reference to loss of reproductive integrity 



Witkin (1956) showed that the yield of mutations in certain auxo- 

 trophic bacteria, resulting from exposure to u.v. light, is fixed within 

 the first hour after irradiation at a high or low level by the nutrition 

 of the organisms. Low levels appear to be associated with the inhibition 

 of protein synthesis, and in an extreme case no mutation was observed 

 at all, although the loss of reproductive integrity of the cells was little, 

 if at all, affected. 



Although loss of reproductive integrity in cells exposed either to 

 u.v. light or to X-radiation has not been entirely prevented by any 

 nutritional variants yet tested very marked changes in the slope, and 

 sometimes also in the extrapolation number, of log survival curves 

 have been obtained both by the use of chloramphenicol (Gillies and 

 Alper, 1959) and by cultivation at reduced temperature (Stapleton et al., 

 1953) after irradiation. The shape of the log survival curve may also be 

 greatly modified by control of the pH of the medium in which the cells 

 were cultured before irradiation (Hollaender et al., 1951 ; Stapleton and 

 Adler, personal communication) and in other ways. As a general rule 

 (Alper, 1961), maximum loss of reproductive integrity occurs if cells 

 are caused to grow fast immediately after irradiation by the use of 

 optimal media and optimal temperatures : conversely, more cells survive 

 when gro^^■th is slowed or protein synthesis depressed after irradiation. 

 The yield of interchanges when plant cells are exposed to spaced doses 

 of radiation is increased by the inhibition of respiration or chloram- 

 phenicol treatment between the two irradiations (Wolff, 1959). Nu- 

 tritional control for a period of about an hour before an anoxic irradia- 

 tion may change the yield of interchanges produced in plant cells by a 

 factor of seven (Beatty and Beatty, 1960): This is equivalent to 

 changing the dose by a factor of about 3 since interchanges vary 

 roughly as the square of the dose. Anaerobic metabolism was found to 

 increase the yield, and aerobic metabolism, or the addition of ATP to 

 cells which had been growing anaerobically, to depress the yield. 



The interpretation of these observations is in the province of radia- 

 tion biochemistry, and beyond the scope of this paper. If it be granted 

 that the nutritional control of radiation damage in some way concerns 

 the replacement or repair by normal metabolic processes, of key mole- 

 cules in the DNA-RNA-protein class, which have been damaged 

 through ionization, excitation and radical formation, then the question 

 may be asked whether or not the extent to which damage may be re- 

 paired is the same for all chemical j)athways by which the damage was 

 produced. Alternatively, we may ask if damage which is produced by 



