Isomer-specific acute toxicity and cell proliferation in livers of B6C3F1 mice exposed to dichlorobenzene.

T Umemura, M Saito, A Takagi, Y Kurokawa

Index: Toxicol. Appl. Pharmacol. 137(2) , 268-74, (1996)

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Abstract

The acute hepatotoxicity of isomers of dichlorobenzene (o-, m-, and p-DCB) was compared in livers of male B6C3F1 mice at different time points after a single intragastric administration. The highest doses of o-, m-, and p-DCB administered, 300, 300, and 1800 mg/kg, respectively, are below the lethal range. Acute hepatic injury was assessed by serum alanine aminotransferase (ALT) activity and hepatic histology. Hepatocyte replication was estimated by means of immunohistochemical demonstration of BrdU-labeled cells. Both o-DCB and m-DCB at a dose of 300 mg/kg produced significant elevations of liver weight and ALT activity as well as extensive liver cell necrosis. In contrast, p-DCB at a highest dose of 1800 mg/kg induced slight hepatocyte injury. Dose-response studies indicated that the rank order for acute hepatotoxicity of the isomers was m-DCB > o-DCB > or = p-DCB. However, p-DCB induced hepatocyte cell proliferation in spite of the lack of manifest hepatotoxicity. In contrast, increases of cell proliferation due to o- or m-DCB exposure occurred only after dosages that caused hepatic injury. These data suggest the hepatocyte proliferation induced by o- or m-DCB is compensatory regeneration while that induced by p-DCB is a response to mitogenic stimulation.