Amplification Effect Observed in Interrelated Enzyme Systems after Irradiation

Abstract

According to Latarjet and Gray (1), the development of injury in an irradiated living cell can be divided into four steps. The first step involves the direct interaction between ionizing radiation and the molecules of the cell; the second consists of reactions between short-lived radicals and molecules of biological importance. In the third step, chemical chain reactions amplify the primary radiation damage resulting from the first two stages to the point where the final step, observable injury, is apparent. Observable radiation effects in cells include cytological lesions, genetic damage, and biochemical changes. Although a considerable body of information exists about the first, second, and fourth stages, little is known about the third stage. Gray (2) compared the amplification of the initial injury occurring in the third stage to the breakdown of a machine which is operated in a slightly damaged condition. Similarly, defective function of a damaged cell due to relatively small changes in the concentrations of the reactants in a series of consecutive or competitive reactions would be manifested as large changes in the over-all reaction rates of metabolic processes, and this might lead to cell death. The present experiments were designed to illustrate how partial inactivation by irradiation of one or more components of an enzyme system affects the reaction rate of the complete system. Although some aspects of reaction kinetics are ignored for the purpose of simplification, this type of experiment is, at least, one step closer to the situation existing in the living cells than the conditions usually used in in vitro experiments on radiation inactivation of one-step enzyme systems. In each experiment, the concentration of the two components to be irradiated was chosen so as to be rate-limiting. By this it is meant that the initial rate of