Responses of cells to radiation sensitizers: methods of analysis

Several well-known transforms of the widely-used Michaelis-Menten function linearize the kinetics of many competition reactions such as enzymatic processes. These transforms allow easy and accurate evaluation of the mathematical constants of the system, as well as giving clues to the various mechanisms involved in these competitions. In this paper these linearization techniques are applied to several sets of data from several authors that describe the radiation sensitivity determined by varied concentrations of two sensitizers--O2 and misonidazole. It is shown that, when the increment in sensitivity determined at the various concentrations of sensitizer is used as the dependent variable, straight lines are obtained from various sets of data when either the so-called Lineweaver-Burk or the Eadie-Hofstee transform is used. The E-H transform results in a better distribution of data points and, accordingly, is preferred. The transform allows recognition of two oxygen-dependent processes (one at low [O2] and one at high [O2]) in data apparently demonstrating but one; and, as well, two processes determined at two levels of misonidazole from data that appeared to describe one. These results support the evidence given earlier for two oxygen effects in other cells. Also, the transform reveals that in different cell systems two inhibitors of the oxygen effect appear to act in the same manner on one oxygen effect and in a different way on the other. In discussion the value of the transform in analysing mechanisms of sensitization is examined, and its further potential use in understanding the action of chemical protective agents is pointed out.