APOPTOSIS OF MURINE HEPATOCYTES INDUCED BY HIGH-DOSES OF GALACTOSAMINE

Apoptosis induced by high doses of Galactosamine (GalN) was investigat ed in mice hepatocytes in vivo. In mice intraperitoneally (ip) 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 an d eosin (HE)-stained sections and TUNEL-positive cells were markedly f ound at 24 hr PA. At 48 hr PA, cellular degeneration and necrosis of h epatocytes were prominently observed, and TUNEL-positive cells were sc arcely found. In the mice ip treated with GalN 1.5 g/kg, the lesion wa s milder Acidophilic bodies and TUNEL-positive cells were scarcely fou nd at 24 hr PA, whereas they were markedly seen at 48 hr PA. In additi on, a ladder-like DNA fragmentation pattern by agarose gel electrophor esis was observed most remarkably at 24 hr PA with GalN 3 g/kg and at 48 h-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 prominen tly 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 sub sequently by necrosis in vivo.