FLASH-RT does not affect chromosome translocations and junction structures beyond that of CONV-RT dose-rates.

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-prox

SUBMITTER: Barghouth PG 

PROVIDER: S-EPMC10081175 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature