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A Functional Immune System Is Required for the Systemic Genotoxic Effects of Localized Irradiation.

Pavel N Lobachevsky1, Jessica Ventura2, Lina Giannakandropoulou3

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The immune system propagates radiation-induced abscopal effects (RIAEs), causing DNA damage and apoptosis in distant tissues. Immune disruption abrogates these systemic genotoxic effects, highlighting the immune system's role in radiation response.

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Area of Science:

  • Radiobiology
  • Immunology
  • Genetics

Background:

  • Nontargeted effects of ionizing radiation, known as radiation-induced abscopal effects (RIAEs), involve damage to unirradiated cells and tissues.
  • RIAEs include DNA damage, apoptosis, and immune responses, even in normal tissues distant from the irradiation site.
  • Previous studies demonstrated RIAEs in mice following localized irradiation.

Purpose of the Study:

  • To investigate the specific components of the immune system responsible for generating radiation-induced abscopal effects (RIAEs).
  • To determine the role of macrophages and chemokine signaling in the propagation of systemic genotoxic effects after localized radiation exposure.

Main Methods:

  • Irradiation of localized regions in immune-deficient mice models: SCID/IL2γR-/- (NSG) mice, macrophage-depleted wild-type C57BL6/J mice, and chemokine ligand 2/monocyte chemotactic protein 1 null mice.
  • Assessment of DNA double-strand breaks, oxidatively induced clustered DNA lesions, and apoptosis in tissues distant from the irradiation site.
  • Comparison of RIAE endpoints between immune-disrupted mice and wild-type C57BL6/J mice.

Main Results:

  • Wild-type mice exhibited DNA damage and apoptosis in distant tissues, confirming the RIAE model.
  • These abscopal effects were significantly reduced or eliminated in mice with disrupted immune systems.
  • The findings indicate a critical role for the immune system in mediating systemic genotoxic effects following localized irradiation.

Conclusions:

  • The immune system is pivotal in the propagation of radiation-induced abscopal effects.
  • Understanding these immune mechanisms is crucial for developing strategies to mitigate systemic radiation toxicity.
  • Further research is needed to fully elucidate the interplay between radiation and the immune system for improved therapeutic outcomes.