Gold nanoparticles are considered as promising agents to increase radiosensitization. However, the mechanisms of the biological enhancement effects resulting from physical dose enhancement, reactions of chemical radical species and radiobiological repair mechanisms are still under investigation. In this study, we have developed a new multi-scale methodology for MC simulations of radiation induced DNA damage in vivo. A voxel mouse model irradiated by either 100 kVp or 200 kVp x-ray beams constitutes the macroscopic scale (mouse and tumor). To simulate the effects of AuNPs inside a cell, phase spaces were employed to transfer particles to the microscopic scale, which consists of a cell geometry including a detailed DNA model. Results are calculated both with and without AuNPs to study radiosensitizing effects. An AuNP induced enhancement of both dose and DNA strand breaks has been established for all scenarios. Produced chemical radicals including hydroxyl molecules, which are responsible for DNA damage, were found to be significantly increased. We further observed a dependency of the results on the location of the cells within the tumor for 200 kVp x-rays. Our new methodology allows the individual adjustment of parameters in each simulation step and can now be applied to other studies investigating the radiosensitizing effects of AuNPs on living cells.