<i>In vivo</i> formation and repair of DNA double-strand breaks after computed tomography examinations

TLDR

Ionizing radiation can induce cancer, largely through DNA double‑strand breaks, which are the most harmful lesions produced. The study quantified γ‑H2AX foci in lymphocytes from patients undergoing thoracic or abdominal CT scans to measure in vivo DSBs. DSB numbers increased linearly with the dose–length product, and foci resolved to background in healthy subjects, whereas a patient with prior radiotherapy toxicity showed persistently high foci and a confirmed repair defect, demonstrating that diagnostic CT can reveal individual DSB repair capacity.

Abstract

Ionizing radiation can lead to a variety of deleterious effects in humans, most importantly to the induction of cancer. DNA double-strand breaks (DSBs) are among the most significant genetic lesions introduced by ionizing radiation that can initiate carcinogenesis. We have enumerated γ-H2AX foci as a measure for DSBs in lymphocytes from individuals undergoing computed tomography examination of the thorax and/or the abdomen. The number of DSBs induced by computed tomography examination was found to depend linearly on the dose–length product, a radiodiagnostic unit that is proportional to both the local dose delivered and the length of the body exposed. Analysis of lymphocytes sampled up to 1 day postirradiation provided kinetics for the in vivo loss of γ-H2AX foci that correlated with DSB repair. Interestingly, in contrast to results obtained in vitro , normal individuals repair DSBs to background levels. A patient who had previously shown severe side effects after radiotherapy displayed levels of γ-H2AX foci at various sampling times postirradiation that were several times higher than those of normal individuals. γ-H2AX and pulsed-field gel electrophoresis analysis of fibroblasts obtained from this patient confirmed a substantial DSB repair defect. Additionally, these fibroblasts showed significant in vitro radiosensitivity. These data show that the in vivo induction and repair of DSBs can be assessed in individuals exposed to low radiation doses, adding a further dimension to DSB repair studies and providing the opportunity to identify repair-compromised individuals after diagnostic irradiation procedures.