Manaka Yuya, Kusumoto-Matsuo Rika, Matsuno Yusuke, Asai Haruka, Yoshioka Ken-Ichi
Laboratory of Genome Stability Maintenance, National Cancer Center Research Institute, Tsukiji, Chuo-ku, Tokyo, Japan.
Department of NCC Cancer Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Yushima, Bunkyou-ku, Tokyo, Japan.
Heliyon. 2024 Mar 15;10(6):e28044. doi: 10.1016/j.heliyon.2024.e28044. eCollection 2024 Mar 30.
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.
γ射线照射会诱导DNA双链断裂（DSB）并增加癌变风险。受照射的细胞通常直接修复DSB，但会积累与复制应激相关的DSB，从而增加结构变异（SV）的风险。尽管也会诱导单核苷酸变异（SNV），但γ射线照射诱导了哪些SNV仍不清楚。在这里，我们表明单碱基替换（SBS）17a、17b和40特征是由γ射线照射诱导的，这主要是A-T碱基对中的SNV诱导。虽然由基因组不稳定诱导的SNV通常与SV相关，但由γ射线照射诱导的SNV及其相关特征并非如此。由于活性氧（ROS）是SBS17a和17b的可能原因，γ射线照射（1-8 Gy）会诱导ROS，这表明ROS与SNV诱导有关。因此，我们的结果表明，与ROS相关的SNV会因照射而增加，并且与ROS相关的SNV是独立于SV诱导产生的。
