Liver apoptosis after dimethylnitrosamine administration in shrews.
Female house musk shrews (Suncus murinus, Insectivora) were given a single i.p. dose of 30 mg/kg dimethylnitrosamine (DMN) at 8 weeks of age which was lethal 36 to 48 hrs after dosing. Liver tissues were collected from shrews killed 3, 6, 16, 24 and 36 hrs after treatment, and the sequential development of the lesions was characterized. DMN induced acute centrilobular cell injury. In 6 hrs, a few cells became apoptotic in the centrilobular area; the number increased at 16 hrs and 24 hrs, and was prominent at 36 hrs. There was no inflammatory reaction or necrosis and hemorrhage was not obvious. These apoptotic cells as well as normal appearing cells in the centrilobular area were labeled by the TUNEL method. In both hepatocytes and endothelial cells, apoptosis was confirmed electron microscopically as nuclear chromatin condensation at the periphery with no mitochondria swelling. When an i.p. dose of 10 mg/kg DMN was given twice at 8 and 9 weeks of age, no acute toxicity was induced, and the liver of shrews surviving for 50 weeks of age was normal with no tumor formation. These findings indicate that a single i.p. administration of 30 mg/kg DMN induced severe and fatal toxicity on liver tissues in shrews due to apoptosis, whereas 2 x 10 mg/kg DMN had no carcinogenic effect.
Shikata
N
N
Department of Pathology, Kansai Medical University, Osaka, Japan.
Oyaizu
T
T
Senzaki
H
H
Uemura
Y
Y
Tsubura
A
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004128:Dimethylnitrosamine / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects*; D012788:Shrews
D004128:Dimethylnitrosamine