Shikata N, Oyaizu T, Senzaki H, Uemura Y, Tsubura A
Department of Pathology, Kansai Medical University, Osaka, Japan.
Exp Toxicol Pathol. 1996 Jun;48(4):307-11. doi: 10.1016/S0940-2993(96)80025-X.
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.
雌性家麝鼩（Suncus murinus，食虫目）在8周龄时腹腔注射一次剂量为30mg/kg的二甲基亚硝胺（DMN），给药后36至48小时致死。在处理后3、6、16、24和36小时处死麝鼩并收集肝脏组织，对病变的连续发展进行特征描述。DMN诱导急性小叶中央细胞损伤。6小时时，小叶中央区域有少数细胞发生凋亡；16小时和24小时时数量增加，36小时时显著。无炎症反应，坏死和出血不明显。通过TUNEL法对小叶中央区域的这些凋亡细胞以及外观正常的细胞进行标记。在肝细胞和内皮细胞中，电子显微镜证实凋亡表现为核染色质周边浓缩，线粒体无肿胀。当在8周龄和9周龄时腹腔注射剂量为10mg/kg的DMN两次时，未诱导急性毒性，存活至50周龄的麝鼩肝脏正常，无肿瘤形成。这些发现表明，腹腔注射一次30mg/kg的DMN由于凋亡对麝鼩肝脏组织诱导了严重的致命毒性，而2×10mg/kg的DMN没有致癌作用。
