Article Dans Une Revue International Journal of Radiation Oncology, Biology, Physics Année : 2020

Stereotactic lung irradiation in mice promotes long-term senescence and lung injury

Mohamedamine Benadjaoud
Morgane dos Santos
  • Fonction : Auteur

Résumé

Purpose: Lung cancer will be treated more frequently using stereotactic body radiation therapy, and preclinical research tomodel long-term toxicity of ablative doses of radiation is crucial. Stereotactic lung irradiation of a small volume can induceradiation pneumonitis and fibrosis in normal tissues. Methods and Materials: Senescence has been reported to contribute to lung fibrosis, and we investigated in vivo the effects ofablative doses of ionizing radiation on senescence-associated processes. The left lung of p16$^{INK4a}$ -LUC knock-in mice wasexposed to a single dose or fractionated radiation doses in a millimetric volume using a small animal radiation research platform. Results: Single or fractionated ablative radiation induces acute and very long-term p16$^{INK4a}$ activation in the irradiated lungtarget volume associated with lung injury. We observed a panel of heterogeneous senescent cells including pneumocytes, macrophages,and endothelial cells that accumulated around the radiation-induced lung focal lesion, suggesting that different senescentcell types may contribute to radiation injury. Conclusions: This work provides important information on the long-term effects of ablative radiation doses in the normal lungand strongly suggests that stress-induced senescence is involved in stereotactic body radiation therapyeinduced late fibrosis.

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Dates et versions

hal-03375546 , version 1 (12-10-2021)

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Citer

Frédéric Soysouvanh, Mohamedamine Benadjaoud, Morgane dos Santos, Michele Mondini, Jeremy Lavigne, et al.. Stereotactic lung irradiation in mice promotes long-term senescence and lung injury. International Journal of Radiation Oncology, Biology, Physics, 2020, 106 (5), pp.1017-1027. ⟨10.1016/j.ijrobp.2019.12.039⟩. ⟨hal-03375546⟩
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