We explore the effects of overdispersed DNA lesion distribution on the shapes
of cell surviving curves of mammalian cells exposed to hadrons at various
doses. To provide a theoretical framework in resolving discrepancies between
experimental data and Linear-quadratic (LQ)model predictions, we employ a
non-Poisson distribution of lethal lesions together with non-homologous
end-joining (NHEJ) pathway of double-strand break (DSB) repair. A negative
binomial (NB)distribution is used to study the effect of the overdispersion on
the shapes and possible reduction of dose-response curvature at high doses. The
error distribution is customized to include an adjustable parameter so that the
overdispersion parameter of NB is not constant but depends on the mean of the
distribution. The trends in predicted cell survival responses are compared with
the experimental data in low and high dose regions at various LET values for
proton, helium, and carbon ions. The cell survival responses calculated by the
present method reveal straightening of survival curves at high doses. This
suggests that the overdispersion causes the cell survival dose-response to
approximate log-linear behaviour at high doses. Comparison of the cell survival
predictions with the Particle Irradiation Data Ensemble (PIDE) shows that the
NB model provides better fits to the experimental data following low and
intermediate doses. Whereas the model predictions are not validated at tiny and
very high doses, nonetheless, the presented approach provides insight into
underlying microscopic mechanisms which may help to improve the radiobiological
responses along the dose-response curves and resolve discrepancies between
experimental data and current cell survival models.Comment: 11 pages, 9 figure