A discrete cell survival model including repair after high dose-rate of ionizing radiation

Abstract

A discrete cell survival model has been developed that is represented by six parameters (gamma,delta,alpha,epsilon,kappa, and t0). It is assumed that, linearly with the dose, two types of lesions are generated, with the number per unit dose described by the parameters gamma and delta. The two types of lesions, irreparable (lethal damage abbreviated as LD) damage and reparable (potentially lethal damage abbreviated as PLD) damage, follow a Poisson statistic. The PLD can be either repaired by an enzymatic process or converted into a lethal damage by a time- and dose-dependent process. For repair of PLD a Michaelis-Menten kinetics has been assumed, described by the maximum velocity alpha of the process and the MichaelisMenten constant, kappa. The unrepaired PLD are fixed and become lethal after replating. The applicability of the model was tested by fitting 11 experimental data sets obtained with different cell lines and variable repair times simulated by delayed plating recovery or inhibition of repair processes by different agents. It has been concluded from the results that the repair process is rather totally than partially saturated. Therefore, the model was adapted by assuming a zero-order reaction for the repair process. Good agreement between model assumptions and molecular mechanisms is obtained by assuming PLD and LD to be double-strand breaks. The model and the results obtained are discussed and compared with published results and experimental data.