Functional and structural alterations of epithelial barrier properties of rat ileum following X-irradiation.
Irradiation of the digestive system leads to alterations of the small intestine. We have characterized the disruption of the barrier integrity in rat ileum from 1 to 14 days following irradiation ranging from 6 to 12 Gy. The intestinal permeability to 14C-mannitol and 3H-dextran 70 000 was measured in vitro in Ussing chambers. In parallel to these functional studies, immunohistochemical analyses of junctional proteins (ZO-1 and beta-catenin) of ileal epithelium were performed by confocal microscopy. Irradiation with 10 Gy induced a marked decrease in epithelial tissue resistance at three days and a fivefold increase in mannitol permeability, without modifications of dextran permeability. A disorganization of the localization for ZO-1 and beta-catenin was also observed. At 7 days after irradiation, we observed a recovery of the organization of junctional proteins in parallel to a return of intestinal permeability to control value. In addition to these time-dependent effects, a gradual effect on epithelial integrity of the radiation doses was observed 3 days after irradiation. This study shows a disruption of the integrity of the intestinal barrier in rat ileum following abdominal X-irradiation, depending on the time postirradiation and on the delivered dose. The loss of barrier integrity was characterized by a disorganization of proteins of tight and adherent junctions, leading to increased intestinal permeability to mannitol.
Dublineau
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I
Institut de Radioprotection et de Sûreté Nucléaire, Direction de la RadioProtection de l'Homme, Service de Radiobiologie et d'Epidemiologie, IRSN, BP 17, F-92262 Fontenay-aux-Roses, CEDEX, France. isabelle.dublineau@irsn.fr
Lebrun
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F
Grison
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S
Griffiths
N M
NM
D000818:Animals; D002463:Cell Membrane Permeability / Q000528:radiation effects; D003911:Dextrans / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D007082:Ileum / Q000473:pathology / Q000528:radiation effects* / Q000648:ultrastructure; D007365:Intercellular Junctions / Q000378:metabolism / Q000528:radiation effects / Q000648:ultrastructure; D007413:Intestinal Mucosa / Q000503:physiopathology / Q000528:radiation effects* / Q000648:ultrastructure; D008297:Male; D008353:Mannitol / Q000378:metabolism; D011832:Radiation Injuries / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D003911:Dextrans; D008353:Mannitol