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Updated: Sep 26, 2025
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Measuring DNA Damage and Repair in Mouse Splenocytes After Chronic In Vivo Exposure to Very Low Doses of Beta- and Gamma-Radiation
Published on: July 3, 2015
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Radiation-Induced Bystander Effect Mediated by Exosomes Involves the Replication Stress in Recipient Cells
Mateusz Smolarz1, Łukasz Skoczylas1, Marta Gawin1
1Maria Skłodowska-Curie National Research Institute of Oncology, 44-102 Gliwice, Poland.
International Journal of Molecular Sciences
|April 23, 2022
Summary
Exosomes from irradiated cells trigger DNA breaks in recipient cells via replication stress, activating ATM and ATR kinases. This bystander effect occurs before significant exosome internalization, suggesting a receptor-mediated mechanism.
Area of Science:
- Cell Biology
- Radiation Oncology
- Molecular Biology
Background:
- The radiation-induced bystander effect involves DNA damage in non-directly irradiated cells.
- Exosomes mediate this effect, but the precise mechanism of DNA damage remains elusive.
Purpose of the Study:
- To elucidate the mechanism by which exosomes from irradiated cells induce DNA damage and replication stress in recipient cells.
Main Methods:
- FaDu cells were stimulated with exosomes from irradiated or mock-irradiated cells.
- Assessed DNA breaks (gamma H2A.X foci), kinase activation (ATM, ATR), DNA synthesis, RNA:DNA hybrids, and protein phosphorylation.
Main Results:
- Exosomes from irradiated cells induced gamma H2A.X foci and activated ATM/ATR kinases in recipient cells.
- Replication stress, suppressed DNA synthesis, and RNA:DNA hybrids were observed.
- Effects preceded significant exosome internalization, suggesting receptor-mediated signaling.
Conclusions:
- Exosomes mediate the radiation-induced bystander effect through replication stress in recipient cells.
- The mechanism involves ATM/ATR activation and occurs via a potentially receptor-mediated pathway.
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