348 SPECULATIONS ON CELLULAR ACTIONS 



makeup, that is initial state, it is clear that we should not be surprised 

 if any of the parameters m, n, r, s, and h should vary with species or 

 strain, such variation being reflected in differences in shape and/or slope 

 of the survival curve. 



Another biological factor known to affect dose-effect relations is phase 

 of mitosis. This factor, like species or strain, involves marked changes 

 in the physical and chemical initial state of the cell, and again it should 

 not be surprising if any of the five parameters varied from phase to phase 

 of mitosis, thus changing either slope or shape of the dose-effect curve or 

 even both. 



The concentration of water in the cell is naturally of prime interest if 

 the radiobiological mechanism involves energy transfer to water mole- 

 cules as in the special model of Fig. 1. With increase in water content, 

 h should increase, and experimentally it has been observed in various 

 radiobiological actions that the slope of the dose-effect curve varies 

 directly (not necessarily linearly) with water concentration. 



Quite a list of simple solutes is known to affect dose-effect relations, 

 for instance oxygen, carbon dioxide, and cysteine. Such simple mole- 

 cules, added to the cell, might conceivably alter the precursor of the 

 decisive entity in such a way as to alter m, or they might change the 

 chemistry of the cell in some fashion to alter n, the number of decisive 

 entities required to constitute a decisive state. (If m or n were altered, 

 then r or s might consequently be altered.) However, in view of the sug- 

 gestive findings of radiation chemistry, we are much more likely to look 

 for an influence on h exerted through a change in relative probabilities of 

 relevant and of competing processes, perhaps at the level of process B 

 or C (Fig. 2). Unfortunately, in the studies to date on influence of 

 chemical modifiers, complete survival curves have very rarely been 

 worked out. However, complete dose-effect curves might be instructive, 

 because distinct changes in shape would indicate changes in m/r 

 or n/s. 



Temperature, in many radiobiological actions, can influence the dose- 

 effect relations. In most of the available papers, the data are not too 

 plentiful, but it appears that the magnitude of the influence differs con- 

 siderably among various radiobiological mechanisms, and sometimes the 

 direction (decrease or increase) also differs. This state of affairs is not 

 too surprising in view of the following considerations. Temperature 

 could intervene in at least two general ways. First, it could change the 

 chemical composition of the ceU. (As a simple example, the respiration 

 rate might change, thus changing the concentration of oxygen or carbon 

 dioxide, and then one of these chemical factors might alter the dose- 

 effect relations as suggested above.) Second, the variation of tempera- 



