Radiation-induced DNA double-strand breaks in cortisol exposed fibroblasts as quantified with the novel foci-integrated damage complexity score (FIDCS)

Wilhelmina E. Radstake, Alessio Parisi, Silvana Ferreira da Silva Miranda, Kiran Gautam, Randy Vermeesen, Emil Rehnberg, Kevin Tabury, Rob Coppes, Marc Jan van Goethem, Sytze Brandenburg, Ulrich Weber, Claudia Fournier, Marco Durante, Bjorn Baselet, Sarah Baatout

Research outputpeer-review

Abstract

Without the protective shielding of Earth’s atmosphere, astronauts face higher doses of ionizing radiation in space, causing serious health concerns. Highly charged and high energy (HZE) particles are particularly effective in causing complex and difficult-to-repair DNA double-strand breaks compared to low linear energy transfer. Additionally, chronic cortisol exposure during spaceflight raises further concerns, although its specific impact on DNA damage and repair remains unknown. This study explorers the effect of different radiation qualities (photons, protons, carbon, and iron ions) on the DNA damage and repair of cortisol-conditioned primary human dermal fibroblasts. Besides, we introduce a new measure, the Foci-Integrated Damage Complexity Score (FIDCS), to assess DNA damage complexity by analyzing focus area and fluorescent intensity. Our results show that the FIDCS captured the DNA damage induced by different radiation qualities better than counting the number of foci, as traditionally done. Besides, using this measure, we were able to identify differences in DNA damage between cortisol-exposed cells and controls. This suggests that, besides measuring the total number of foci, considering the complexity of the DNA damage by means of the FIDCS can provide additional and, in our case, improved information when comparing different radiation qualities.

Original languageEnglish
Article number10400
Pages (from-to)1-15
Number of pages15
JournalScientific Reports
Volume14
Issue number1
DOIs
StatePublished - Dec 2024

Funding

This work received funding from ESA/BELSPO/Prodex, grant number PEA_4000140806 (IMPULSE). Proton and carbon ion irradiation was performed at the UMCG-PARTREC facility in Groningen, the Netherlands; financed through the ESA-CORA-IBER (19M09) program. Iron irradiation was performed at GSI in Darmstadt, Germany; financed through the ESA-IBER (AO-2019-IBER) program.

FundersFunder number
GSI Helmholtzzentrum für Schwerionenforschung

    ASJC Scopus subject areas

    • General

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