title: Long-term pathological and immunohistochemical features in the liver after intraoperative whole-liver irradiation in rats.
abstract: Radiation therapy (RT) has become particularly important recently for treatment of liver tumors, but there are few experimental investigations pertaining to radiation-induced liver injuries over long-term follow-up periods. Thus, the present study examined pathological liver features over a 10-month period using an intraoperative whole-liver irradiation model. Liver function tests were performed in blood samples, whereas cell death, cell proliferation, and fibrotic changes were evaluated pathologically in liver tissues, which were collected from irradiated rats 24 h, 1, 2, 4 and 40 weeks following administration of single irradiation doses of 0 (control), 15 or 30 Gy. The impaired liver function, increased hepatocyte number, and decreased apoptotic cell proportion observed in the 15 Gy group, but not the 30 Gy group, returned to control group levels after 40 weeks; however, the Ki-67 indexes in the 15 Gy group were still higher than those in the control group after 40 weeks. Azan staining showed a fibrotic pattern in the irradiated liver in the 30 Gy group only, but the expression levels of alpha smooth muscle actin (α-SMA) and transforming growth factor-beta 1 (TGF-β1) in both the 15 and 30 Gy groups were significantly higher than those in the control group (P < 0.05). There were differences in the pathological features of the irradiated livers between the 15 Gy and 30 Gy groups, but TGF-β1 and α-SMA expression patterns supported the gradual progression of radiation-induced liver fibrosis in both groups. These findings will be useful in the future development of protective drugs for radiation-induced liver injury.
authors.affiliation: Department of Radiation Oncology, Gunma University, Graduate School of Medicine, 3-39-22 Showa, Maebashi, Gunma 371-8511, Japan.
authors.forename: Masumi
authors.initials: M
authors.lastname: Imaeda
authors.affiliation: Department of Radiation Oncology, University of Tsukuba, Faculty of Medicine, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan hishikawa@pmrc.tsukuba.ac.jp.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ishikawa
authors.affiliation: Department of Radiation Oncology, Gunma University, Graduate School of Medicine, 3-39-22 Showa, Maebashi, Gunma 371-8511, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Department of Radiation Oncology, Saitama Medical University, 1981 Kamodatsujido, Kawagoe, Saitama 350-8550, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Radiation Oncology, Gunma University, Graduate School of Medicine, 3-39-22 Showa, Maebashi, Gunma 371-8511, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ohkubo
authors.affiliation: Department of Radiation Oncology, Gunma University, Graduate School of Medicine, 3-39-22 Showa, Maebashi, Gunma 371-8511, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Musha
authors.affiliation: Department of Radiation Oncology, Gunma University, Graduate School of Medicine, 3-39-22 Showa, Maebashi, Gunma 371-8511, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Komachi
authors.affiliation: Department of Pathology, Hidaka Hospital, 886 Nakao, Takasaki, Gunma 370-0001, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakazato
authors.affiliation: Department of Radiation Oncology, Gunma University, Graduate School of Medicine, 3-39-22 Showa, Maebashi, Gunma 371-8511, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakano
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D018450:Disease Progression; D004307:Dose-Response Relationship, Radiation; D007150:Immunohistochemistry; D007432:Intraoperative Period; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D008103:Liver Cirrhosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008297:Male; D011833:Radiation Injuries, Experimental / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000199:Actins; D053773:Transforming Growth Factor beta1; C498862:Acta2 protein, rat
keywords: alpha smooth muscle actin; apoptosis; liver fibrosis; radiation-induced liver injury; transforming growth factor-beta 1