Single base substitution signatures 17a, 17b, and 40 are induced by γ-ray irradiation in association with increased reactive oxidative species

Abstract

γ-Ray irradiation induces DNA double strand breaks (DSBs) and increases the risk of cancerization. Irradiated cells usually repair DSBs directly, but accumulate replication stress-associated DSBs, increasing the risk of structural variants (SVs). Although single nucleotide variants (SNVs) are also induced, it is still unclear which SNVs are induced by γ-ray irradiation. Here, we show that single base substitution (SBS) 17a, 17b, and 40 signatures were induced by γ-ray irradiation, which is mainly SNV induction in A-T bps. While SNVs induced by genomic instability were usually associated with SVs, SNVs induced by γ-ray irradiation and the associated signatures were not. As reactive oxygen species (ROS) are a possible cause of SBS17a and 17b, ROS were induced upon γ-ray irradiation (1–8 Gy), indicating the association of ROS for the SNV induction. Thus, our results reveal that ROS-associated SNVs are increased by irradiation, and that ROS-associated SNVs are induced independently of SVs.