title: Hepatic regeneration after sublethal partial liver irradiation in cirrhotic rats.
abstract: Our previous animal study had demonstrated that partial liver irradiation (IR) could stimulate regeneration in the protected liver, which supported the measurements adopted in radiotherapy planning for hepatocellular carcinoma. The purpose of this present study is to investigate whether cirrhotic liver repopulation could be triggered by partial liver IR. The cirrhosis was induced by thioacetamide (TAA) in rats. After cirrhosis establishment, TAA was withdrawn. In Experiment 1, only right-half liver was irradiated with single doses of 5 Gy, 10 Gy and 15 Gy, respectively. In Experiment 2, right-half liver was irradiated to 15 Gy, and the left-half to 2.5 Gy, 5 Gy and 7.5 Gy, respectively. The regeneration endpoints, including liver index (LI); mitotic index (MI); liver proliferation index (LPI); PCNA-labeling index (PCNA-LI); serum HGF, VEGF, TGF-α and IL-6, were evaluated on 0 day, 30-day, 60-day, 90-day, 120-day and 150-day after IR. Serum and in situ TGF-β1 were also measured. In both experimental groups, the IR injuries were sublethal, inducing no more than 9% animal deaths. Upon TAA withdrawal, hepatic regeneration decelerated in the controls. In Experiment 1 except for LI, all other regeneration parameters were significantly higher than those in controls for both right-half and left-half livers. In Experiment 2 all regeneration parameters were also higher compared with those in controls for both half livers. Serum HGF and VEGF were increased compared with that of controls. Both unirradiated and low dose-irradiated cirrhotic liver were able to regenerate triggered by sublethal partial liver IR and higher doses and IR to both halves liver triggered a more enhanced regeneration.
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Gu
authors.forename: Song-Tao
authors.initials: ST
authors.lastname: Lai
authors.forename: Ning-Yi
authors.initials: NY
authors.lastname: Ma
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Zhao
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Ren
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.forename: Guo-Liang
authors.initials: GL
authors.lastname: Jiang
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000532:radiotherapy; D004307:Dose-Response Relationship, Radiation; D017228:Hepatocyte Growth Factor / Q000097:blood; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008106:Liver Cirrhosis, Experimental / Q000473:pathology / Q000503:physiopathology / Q000532:radiotherapy*; D008113:Liver Neoplasms / Q000532:radiotherapy; D008115:Liver Regeneration / Q000528:radiation effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016211:Transforming Growth Factor alpha / Q000097:blood; D053773:Transforming Growth Factor beta1 / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D016211:Transforming Growth Factor alpha; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D017228:Hepatocyte Growth Factor