title: Rat model of fractionated (2 Gy/day) 60 Gy irradiation of the liver: long-term effects.
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.
authors.affiliation: Department of Radiotherapy, University Medical Center, Göttingen, Germany.
authors.forename: Margret
authors.initials: M
authors.lastname: Rave-Fränk
authors.forename: Ihtzaz Ahmed
authors.initials: IA
authors.lastname: Malik
authors.forename: Hans
authors.initials: H
authors.lastname: Christiansen
authors.forename: Naila
authors.initials: N
authors.lastname: Naz
authors.forename: Sadaf
authors.initials: S
authors.lastname: Sultan
authors.forename: Ahmad
authors.initials: A
authors.lastname: Amanzada
authors.forename: Martina
authors.initials: M
authors.lastname: Blaschke
authors.forename: Silke
authors.initials: S
authors.lastname: Cameron
authors.forename: Shakil
authors.initials: S
authors.lastname: Ahmad
authors.forename: Clemens Friedrich
authors.initials: CF
authors.lastname: Hess
authors.forename: Giuliano
authors.initials: G
authors.lastname: Ramadori
authors.forename: Federico
authors.initials: F
authors.lastname: Moriconi
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D007770:L-Lactate Dehydrogenase / Q000097:blood; D007958:Leukocyte Count; D008099:Liver / Q000473:pathology / Q000528:radiation effects*; D008297:Male; D009929:Organ Size / Q000528:radiation effects; D011829:Radiation Dosage; D011839:Radiation, Ionizing; D051381:Rats; D017208:Rats, Wistar; D013995:Time; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: C576839:TIMP1 protein, rat; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D007770:L-Lactate Dehydrogenase; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase