| Title: |
Modulation of cellular responses to X-ray irradiation : a bio-inspired approach based on the hibernating brown bear model ; Modulation des réponses cellulaires aux irradiations X : approche bio-inspirée sur le modèle de l'ours brun hibernant |
| Authors: |
Sutter, Jade |
| Contributors: |
Laboratoire de Physique de Clermont (LPC); Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA); Université Clermont Auvergne; Patrick Vernet; Fabrice Bertile |
| Source: |
https://theses.hal.science/tel-05627316 ; Cancer. Université Clermont Auvergne, 2025. Français. ⟨NNT : 2025UCFA0180⟩. |
| Publisher Information: |
CCSD |
| Publication Year: |
2025 |
| Collection: |
HAL-IN2P3 (Institut national de physique nucléaire et de physique des particules) |
| Subject Terms: |
Omics; Hibernation; Brown bear; Radiation; Omiques; Ours brun; Rayonnements; [SDV.CAN]Life Sciences [q-bio]/Cancer |
| Description: |
Torpor is characterized by a profound metabolic slowdown, which can last from several days to several months in the case of hibernation. This physiological state has been associated with natural protection against ionizing radiation in small hibernating mammals. Understanding the mechanisms underlying this tolerance could lead to the development of new radiation protection strategies for humans, particularly for personnel working in radioactive environments. Furthermore, brown bear serum collected during hibernation has been shown to exert anti-proteolytic effects on cultured human muscle cells, thus reproducing certain characteristics of hibernation in vitro. In this thesis, we therefore evaluated the ability of serum from hibernating and non-hibernating bears to modulate the cellular response to ionizing radiation.A first large-scale approach using irradiated and non-irradiated healthy human fibroblast cells (HFF-1) revealed that incubation with bear serum induces profound remodeling of the cellular proteome, with signs of an anti-fibrotic phenotype. Furthermore, our results suggest that this response involves a wide variety of proteins rather than a single metabolic pathway. Functional analysis after X-ray exposure showed a radiosensitizing effect associated with hibernating bear serum on the HFF-1 cell line. Exploration of the mechanisms involved revealed cell cycle alterations, some disruptions in DNA double-strand break repair, and mitochondrial alterations. When the experiments were extended to a human tumor cell line (PC3), no radiosensitizing effect was observed under incubation conditions in the presence of hibernating bear serum, highlighting a strong dependency on the cell line and opening the door to new hypotheses regarding the mechanisms of radiosensitization.In conclusion, the study of the effects of hibernating bear serum on human cells has revealed potential radiosensitization mechanisms. These observations open up interesting avenues for radiotherapeutic research, but their clinical relevance ... |
| Document Type: |
doctoral or postdoctoral thesis |
| Language: |
French |
| Relation: |
NNT: 2025UCFA0180 |
| DOI: |
10.70675/1501dcdfz82d4z4c7fzbe65zbbc1d7559bbf |
| Availability: |
https://theses.hal.science/tel-05627316; https://theses.hal.science/tel-05627316v1/document; https://theses.hal.science/tel-05627316v1/file/2025UCFA0180_SUTTER.pdf; https://doi.org/10.70675/1501dcdfz82d4z4c7fzbe65zbbc1d7559bbf |
| Rights: |
https://about.hal.science/hal-authorisation-v1/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.31ADD65D |
| Database: |
BASE |