{"doi":"10.1101/2023.03.27.534408","title":"FLASH-RT does not affect chromosome translocations and junction structures beyond that of CONV-RT dose-rates","abstract":"Abstract The molecular and cellular mechanisms driving the enhanced therapeutic ratio of ultra-high dose-rate radiotherapy (FLASH-RT) over slower conventional (CONV-RT) radiotherapy dose-rate remain to be elucidated. However, attenuated DNA damage and transient oxygen depletion are among several proposed models. Here, we tested whether FLASH-RT under physioxic (4% O 2 ) and hypoxic conditions (≤2% O 2 ) reduces genome-wide translocations relative to CONV-RT and whether any differences identified revert under normoxic (21% O 2 ) conditions. We employed high-throughput rejoin and genome-wide translocation sequencing ( HTGTS-JoinT-seq ), using S. aureus and S. pyogenes Cas9 “bait” DNA double strand breaks (DSBs), to measure differences in bait-proximal repair and their genome-wide translocations to “prey” DSBs generated by electron beam CONV-RT (0.08-0.13Gy/s) and FLASH-RT (1×10 2 -5×10 6 Gy/s), under varying ionizing radiation (IR) doses and oxygen tensions. Normoxic and physioxic irradiation of HEK293T cells increased translocations at the cost of decreasing bait-proximal repair but were indistinguishable between CONV-RT and FLASH-RT. Although no apparent increase in chromosome translocations was observed with hypoxia-induced apoptosis, the combined decrease in oxygen tension with IR dose-rate modulation did not reveal significant differences in the level of translocations nor in their junction structures. Thus, Irrespective of oxygen tension, FLASH-RT produces translocations and junction structures at levels and proportions that are indistinguishable from CONV-RT.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":391730,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9653,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":259285,"name":"Stavros Melemenidis","orcid":"0000-0002-3941-8784","position":1,"is_corresponding":false},{"id":232789,"name":"Pierre Montay‐Gruel","orcid":"0000-0003-0623-1355","position":2,"is_corresponding":false},{"id":234490,"name":"Jonathan Ollivier","orcid":null,"position":3,"is_corresponding":false},{"id":447205,"name":"Vignesh Viswanathan","orcid":"0000-0001-8307-9508","position":4,"is_corresponding":false},{"id":234488,"name":"Patrik Gonçalves Jorge","orcid":null,"position":5,"is_corresponding":false},{"id":259277,"name":"Luis Soto","orcid":"0000-0001-6244-6081","position":6,"is_corresponding":false},{"id":940018,"name":"Brianna Lau","orcid":"0000-0003-1195-6596","position":7,"is_corresponding":false},{"id":1065472,"name":"Cheyenne Sadeghi","orcid":"0000-0001-5018-2891","position":8,"is_corresponding":false},{"id":1066079,"name":"Anushka Edlabadkar","orcid":null,"position":9,"is_corresponding":false},{"id":259280,"name":"Rakesh Manjappa","orcid":"0000-0001-9681-9210","position":10,"is_corresponding":false},{"id":259278,"name":"Jinghui Wang","orcid":"0000-0001-8126-0530","position":11,"is_corresponding":false},{"id":689711,"name":"Marie Le Bouteiller","orcid":"0000-0002-4149-8488","position":12,"is_corresponding":false},{"id":377352,"name":"Murat Sürücü","orcid":"0000-0003-1693-6850","position":13,"is_corresponding":false},{"id":259284,"name":"Amy S. Yu","orcid":"0000-0002-9730-5593","position":14,"is_corresponding":false},{"id":261254,"name":"Karl Bush","orcid":null,"position":15,"is_corresponding":false},{"id":259282,"name":"Lawrie Skinner","orcid":"0000-0001-7317-1642","position":16,"is_corresponding":false},{"id":252128,"name":"Peter G. Maxim","orcid":"0000-0002-8244-2042","position":17,"is_corresponding":false},{"id":252135,"name":"Billy W. Loo","orcid":"0000-0002-2521-0544","position":18,"is_corresponding":false},{"id":232800,"name":"Charles L. Limoli","orcid":"0000-0002-1321-4142","position":19,"is_corresponding":false},{"id":232801,"name":"Marie‐Catherine Vozenin","orcid":"0000-0002-2109-8073","position":20,"is_corresponding":false},{"id":626395,"name":"Richard L. Frock","orcid":"0000-0001-6963-4931","position":21,"is_corresponding":false},{"id":408940,"name":"Paul G. Barghouth","orcid":"0000-0002-9891-9941","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T01:18:47.408273Z","pmid":"37034651","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}