A mechanistic simulation of induced DNA damage in a bacterial cell by X- and gamma rays: a parameter study

Mechanistic Monte Carlo simulations calculating DNA damage caused by ionizing radiation are highly dependent on the simulation parameters. In the present study, using the Geant4-DNA toolkit, the impact of different parameters on DNA damage induced in a bacterial cell by X- and gamma-ray irradiation was investigated. Three geometry configurations, including the simple (without DNA details), the random (a random multiplication of identical DNA segments), and the fractal (a regular replication of DNA segments using fractal Hilbert curves), were simulated. Also, three physics constructors implemented in Geant4-DNA, i.e., G4EmDNAPhysics_option2, G4EmDNAPhysics_option4, and G4EmDNAPhysics_option6, with two energy thresholds of 17.5 eV and 5-37.5 eV were compared for direct DNA damage calculations. Finally, a previously developed mathematical model of cell repair called MEDRAS (Mechanistic DNA Repair and Survival) was employed to compare the impact of physics constructors on the cell survival curve. The simple geometry leads to undesirable results compared to the random and fractal ones, highlighting the importance of simulating complex DNA structures in mechanistic simulation studies. Under the same conditions, the DNA damage calculated in the fractal geometry was more consistent with the experimental data. All physics constructors can be used alternatively with the fractal geometry, provided that an energy threshold of 17.5 eV is considered for recording direct DNA damage. All physics constructors represent a similar behavior in generating cell survival curves, although the slopes of the curves are different. Since the inverse of the slope of a bacterial cell survival curve (i.e., the D₁₀-value) is highly sensitive to the simulation parameters, it is not logical to determine an optimal set of parameters for calculating the D₁₀-value by Monte Carlo simulation.