title: Apoptosis of murine hepatocytes induced by high doses of galactosamine.
abstract: Apoptosis induced by high doses of Galactosamine (GalN) was investigated in mice hepatocytes in vivo. In mice intraperitoneally (i.p.) treated with GalN 3 g/kg, the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells were first observed at 6 hr postadministration (PA). Both acidophilic bodies in hematoxylin and eosin (HE)-stained sections and TUNEL-positive cells were markedly found at 24 hr PA. At 48 hr PA, cellular degeneration and necrosis of hepatocytes were prominently observed, and TUNEL-positive cells were scarcely found. In the mice ip treated with GalN 1.5 g/kg, the lesion was milder than that in those treated with GalN 3 g/kg. Acidophilic bodies and TUNEL-positive cells were scarcely found at 24 hr PA, whereas they were markedly seen at 48 hr PA. In addition, a ladder-like DNA fragmentation pattern by agarose gel electrophoresis was observed most remarkably at 24 hr PA with GalN 3 g/kg and at 48 hr PA with GalN 1.5 g/kg, and less distinctly at 48 hr PA with GalN 3 g/kg. On the other hand, sGOT and sGPT activities increased prominently at 48 hr PA with GalN 3 g/kg. These results suggest that the cell death induced by high dose of GalN may be caused by apoptosis, and subsequently by necrosis in vivo.
authors.affiliation: Department of Biomedical Science, Faculty of Agriculture, University of Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Tsutsui
authors.forename: K
authors.initials: K
authors.lastname: Hirasawa
authors.forename: M
authors.initials: M
authors.lastname: Takeda
authors.forename: S
authors.initials: S
authors.lastname: Itagaki
authors.forename: S
authors.initials: S
authors.lastname: Kawamura
authors.forename: K
authors.initials: K
authors.lastname: Maeda
authors.forename: T
authors.initials: T
authors.lastname: Mikami
authors.forename: K
authors.initials: K
authors.lastname: Doi
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel / Q000379:methods / Q000662:veterinary; D005688:Galactosamine / Q000008:administration & dosage / Q000494:pharmacology*; D006651:Histocytochemistry / Q000379:methods; D007274:Injections, Intraperitoneal / Q000662:veterinary; D008099:Liver / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D008107:Liver Diseases / Q000097:blood / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron / Q000379:methods / Q000662:veterinary; D009336:Necrosis; D013997:Time Factors
chemical_list: D005688:Galactosamine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase