抄録
Acute and chronic toxicity of a synthetic sydnone derivative, 3-benzylsydnone-4-acetamide (BSA), was examined. Hepatotoxic effect of BSA given in drinking water at concentrations up to 0.2% for 4 weeks varies considerably in differing strains of mice, DDD is the most susceptible followed by C57BL/6, DBA, BALB/c, and ICR. C3H mice were resistant at the tested doses. Female mice were more susceptible than the males in all strains. In DDD females liver cell necrosis developed in 2 weeks with 0.05 to 0.2% BSA in drinking water. With continuous administration of 0.05% BSA liver cell nuclei with polyploid DNA contents (8c, 16c, and 32c) increased in 2 weeks. Then hepatocytes having diploid nuclei predominated in 4 weeks. In DDD female mice hepatocellular carcinoma developed within 12 months with 0.01% and 0.02% of BSA in the drinking water. The incidence was 11.8 and 46.2%, respectively. By whole body autoradiography of female DDD mice given orally 10μCi of [14C]-labeled BSA (about 60mg/kg body weight) the radioactivity was shown to concentrate in the liver after 45min and remained faintly but definitely up to 72 hrs, indicating the possible accumulation of the drug or its metabolite(s) in the liver.
