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The effects of ionizing radiation on the structure and function of the epithelial intestinal cell .

Céline HATON, Doctorate thesis of the University of Paris VI, 168 p., defended in 29th june 2005.

Document type > *Mémoire/HDR/Thesis

Keywords > colon, radiological protection, radiotherapy


Authors > HATON Céline

Publication Date > 29/06/2005


The intestinal mucosa is a particularly radiation-sensitive tissue and damage may occur following either accidental or therapeutic exposure. The deleterious actions of ionising radiation are linked to the formation of sometimes overwhelming quantities of reactive oxygen species (ROS). Production of ROS is both direct and indirect from the secondary effects of irradiation. A better comprehension of the underlying mechanisms of injury will lead to more adapted therapeutic approaches to limit the harmful effects of irradiation. The homeostasis of the intestinal epithelium is regulated by three factors: proliferation, apoptosis and differentiation. These three factors were studied using the cell model. HT29, in order to analyze modulations of this balance after irradiation. Our results. in agreement with other data. showed the establishment of mitotic delay. This arrest of proliferation was followed by apoptosis that in this cell-line depended strongly on mitochondrial alterations. Apoptosis appears to be the major mechanism leading to cell death in this model. Thus, for the first time.
we have shown that irradiated intestinal epithelial cells preserve their capacity to differentiate.
This indicates, although indirectly. that intestinal cells have and preserve an intrinsic capacity restore a functional epithelium. ROS are considered as intermediates between the physical nature of radiations and biological responses. it seems essential to understand anti-oxidant mechanisms used by the cell for defence against the deleterious etTects of ROS post exposurc.
This study of several anti-oxidant defence mechanisms of intestinal mucosa, was carried out in vivo in the mouse at different times following abdominal irradiation. We obscerved an carly mitochondrial response in the hours following the irradiation revealing this organelle as a particular target. We demonstrated a strong alteration of anti-oxidant capacity as revealed by a decrease in SODs. catalasc and an increase of the GPXs and MTs. A part of these modifications appeared to depend on an irradiation-induced inflammatory response. Finally.
we showed that the loss of catalase is linked to the onset of structural damage to the mucosa.
All of these results orient therapeutic strategies towards inducing the proliferation of crypt cells. rather than an inhibition of apoptosis. since the epithelial cells retain differentiation capacity and so production of functional cells.

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Marc Benderitter, Thesis supervisor


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