PURPOSE: To examine the p38 mitogen-activated protein kinase (p38) phosphorylation and transforming growth factor beta 1 (TGF-β1) expression in rat colon enterocytes after irradiation and their contribution to pathology of intestinal radiation disease. MATERIALS AND METHODS: Male Wistar rats were irradiated with whole body γ-radiation of 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10 Gy ((60)Co, 1.44 Gy.min(-1)). Samples were taken 4 and 24 h after irradiation, immunohistochemically stained, then p38 phosphorylation and TGF-β1 expression were measured in apical and cryptal enterocytes using computer image analysis. In selected groups, morphometric parameters, mitosis and apoptosis were evaluated. RESULTS: P38 phosphorylation integrated optical density (IOD)-based levels increased 2.4-fold (p ≤ 0.01) and 3.6 to 22.8-fold (p ≤ 0.001) in apical enterocytes 4 h after 0.5 Gy and 24 h after 3-10 Gy, respectively. TGF-β1 IOD-based expression increased 3.3- to 6.9-fold (p ≤ 0.001) and 1.6- to 4.9-fold (p ≤ 0.001) in apical cells 4 h after 0.5-2, 4, 5 Gy and 24 h after 6-10 Gy, respectively. No changes were observed in crypts. CONCLUSIONS: We found a chronological and dose-dependent order of p38 activation and TGF-β1 expression in apical enterocytes. Transient up-regulation of p38 and TGF-β1 signalling observed 4 h after low-dose irradiation may participate in molecular mechanisms creating cellular over-expression in apical compartment, while persistent patterns measured 24 h after high-dose irradiation might provide protection of remaining cells in order to maintain tissue integrity.
- MeSH
- aktivace enzymů účinky záření MeSH
- apoptóza účinky záření MeSH
- časové faktory MeSH
- celotělové ozáření škodlivé účinky MeSH
- enterocyty cytologie enzymologie metabolismus účinky záření MeSH
- fosforylace účinky záření MeSH
- kolon cytologie účinky záření MeSH
- krysa rodu rattus MeSH
- mitogenem aktivované proteinkinasy p38 metabolismus MeSH
- mitóza účinky záření MeSH
- polarita buněk účinky záření MeSH
- potkani Wistar MeSH
- regulace genové exprese účinky záření MeSH
- záření gama škodlivé účinky MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Gastrointestinal form is the second stage of the Acute Radiation Syndrome (ARS) with a threshold dose of 8 Gy. It represents an absolutely lethal clinical-pathological unit, enteritis necro-hemorrhagica (duodenitis, jejunitis, ileitis, respectively) with unknown causal therapy. The purpose of our study has been to evaluate the morphological changes in a model of radiation-induced enteritis in rats and estimate the significance of changes in biodosimetry. Wistar rats were randomly divided into 21 groups, 10 animals per group. Samples of the jejunum were taken 24, 48, 72, and 96 h after the whole-body gamma-irradiation with the doses of 1, 5, 10, 15, and 20 Gy, and routinely stained with hematoxylin and eosin. Five morphometric markers--intercryptal distance, enterocytal height on the top and base of villus, length of basal lamina of 10 enterocytes and enterocytal width--in irradiated rat jejunum were examined. The results were compared with sham-irradiated control group. After lethal doses of irradiation, all morphometric parameters of jejunum significantly changed. With the exception of intercryptal distance, they might be considered as suitable biodosimetric markers under these experimental conditions. Our morphometry results in radiation-induced jejunitis are in accordance with those in other studies. We were the first who quantified morphological post-irradiation changes in animal jejunum. Some of them might be used under experimental conditions. This experimental study is a predecessor of the clinical assessment of a specific marker. Under clinical practice, the sensitive biodosimetric parameter could serve as one of the guidance for evaluation of the absorbed dose in irradiated troops as well as rescue workers. This is in accordance with tasks and Standardization Agreement of the North Atlantic Treaty Organization.
- MeSH
- bazální membrána patologie účinky záření MeSH
- časové faktory MeSH
- celotělové ozáření MeSH
- enteritida etiologie patologie MeSH
- enterocyty patologie účinky záření MeSH
- experimentální radiační poranění patologie MeSH
- hodnocení rizik MeSH
- jejunum patologie účinky záření MeSH
- krysa rodu rattus MeSH
- nemoci jejuna etiologie patologie MeSH
- potkani Wistar MeSH
- radiometrie MeSH
- vztah dávky záření a odpovědi MeSH
- záření gama MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- MeSH
- akutní nemoc MeSH
- chemotaxe účinky záření MeSH
- chronická nemoc MeSH
- dávka záření MeSH
- enteritida * diagnóza etiologie imunologie patofyziologie patologie MeSH
- enterocyty účinky záření MeSH
- lidé MeSH
- nádorový supresorový protein p53 biosyntéza fyziologie škodlivé účinky MeSH
- radiační poranění * diagnóza etiologie imunologie patofyziologie patologie MeSH
- signální transdukce účinky záření MeSH
- střevní sliznice účinky záření MeSH
- tenké střevo účinky záření MeSH
- Check Tag
- lidé MeSH
