No specific impact of ultra-high dose rates on radiation-induced chromosome rearrangements

Abstract

Ionizing radiation generates DNA double-strand breaks (DSBs) that challenge DNA repair mechanisms and drive mutagenesis, chromosome rearrangements, and cell lethality. These features underlie its application in cancer therapy. DSBs arise from direct DNA ionization or the indirect action of reactive species generated by energy deposition events. While distinct particle-matter interactions are considered independent during standard irradiation timescales, the impact of extreme dose rates—comparable to the reactive species half-lives—remains unclear. Here, we used a chromosome fusion capture (CFC) assay in budding yeast to quantify radiation-induced chromosome rearrangements under varying conditions. We validated the assay’s sensitivity and observed results consistent with prior studies regarding oxygen enhancement ratios and photon energy effects. Importantly, we found that X-rays delivered at extreme dose rates produced chromosome rearrangements at frequencies indistinguishable from standard irradiations. These findings suggest that ultra-high dose rates do not alter the nature or frequency of radiation-induced DSBs, providing insights for FLASH-irradiation protocols.