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Rat model of fractionated (2 Gy/day) 60 Gy irradiation of the liver: long-term effects

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Abstract

The liver is considered a radiosensitive organ. However, in rats, high single-dose irradiation (HDI) showed only mild effects. Consequences of fractionated irradiation (FI) in such an animal model have not been studied so far. Rats were exposed to selective liver FI (total dose 60 Gy, 2 Gy/day) or HDI (25 Gy) and were killed three months after the end of irradiation. To study acute effects, HDI-treated rats were additionally killed at several time points between 1 and 48 h. Three months after irradiation, no differences between FI and HDI treatment were found for macroscopically detectable small “scars” on the liver surface and for an increased number of neutrophil granulocytes distributed in the portal fields and through the liver parenchyma. As well, no changes in HE-stained tissues or clear signs of fibrosis were found around the portal vessels. Differences were seen for the number of bile ducts being increased in FI- but not in HDI-treated livers. Serum levels indicative of liver damage were determined for alkaline phosphatase (AP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (γGT) and lactate dehydrogenase (LDH). A significant increase of AP was detected only after FI while HDI led to the significant increases of AST and LDH serum levels. By performing RT-PCR, we detected up-regulation of matrix metalloproteinases, MMP-2, MMP-9, MMP-14, and of their inhibitors, TIMP-1, TIMP-2 and TIMP-3, shortly after HDI, but not at 3 month after FI or HDI. Overall, we saw punctual differences after FI and HDI, and a diffuse formation of small scars at the liver surface. Lack of “provisional clot”-formation and absence of recruitment of mononuclear phagocytes could be one explanation for scar formation as incomplete repair response to irradiation.

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Acknowledgments

This work was supported by grants from the “Deutsche Krebshilfe” (Project 108774) and from the “Deutsche Forschungsgemeinschaft” (DFG Project MA 5488/2-1). Our special thanks go to Mrs Sonja Heyroth, Mrs Elke Neumann and Mrs Siglinde Zachmann for their skilful assistance.

Conflict of interest

We declare that we have no conflict of interest.

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Author notes

  1. Hans Christiansen

    Present address: Department of Radiotherapy, Hannover Medical School (MHH), Hannover, Germany

Authors and Affiliations

  1. Division of Gastroenterology and Endocrinology, Department of Internal Medicine, University Medical Center, Göttingen, Germany

    Ihtzaz Ahmed Malik, Hans Christiansen, Naila Naz, Ahmad Amanzada, Martina Blaschke, Silke Cameron, Shakil Ahmad, Giuliano Ramadori & Federico Moriconi

  2. Department of Radiotherapy, University Medical Center, Göttingen, Germany

    Margret Rave-Fränk, Hans Christiansen, Sadaf Sultan & Clemens Friedrich Hess

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  1. Margret Rave-Fränk
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Correspondence to Federico Moriconi.

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Margret Rave-Fränk and Ihtzaz Ahmed Malik contributed equally to the work.

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Rave-Fränk, M., Malik, I.A., Christiansen, H. et al. Rat model of fractionated (2 Gy/day) 60 Gy irradiation of the liver: long-term effects. Radiat Environ Biophys 52, 321–338 (2013). https://doi.org/10.1007/s00411-013-0468-7

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  • DOI: https://doi.org/10.1007/s00411-013-0468-7

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