Comparison Of 2,3,7,8-Tetrachlorodibenzo-Para-Dioxin-Mediated Hepatotoxicity In C57bl/6j And Dba/2j Mice

The toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was examined by clinical chemistry and liver histopathology in Ah-responsive C57BL/6J (C57) and Ah-nonresponsive DBA/2J (DBA) mice. Hepatotoxicity was assessed at 1, 3, and 7 d following a single ip injection of TCDD at doses that maximally induce hepatic aryl hydrocarbon hydroxylase (AHH) activity (3-mu-g/kg for C57 and 30-mu-g/kg for DBA mice) and at doses approaching the LD50 (150-mu-g/kg for C57 and 600-mu-g/kg for DBA mice). Histological examination of liver sections was found to be a more sensitive detection method for TCDD-induced hepatic changes than clinical chemistry analyses. Dramatic differences in the development and type of liver injury were observed between TCDD-treated C57 and DBA mice. C57 mice given 3-mu-g TCDD/kg developed mild to moderate hepatic lipid accumulation in the absence of both inflammation and necrosis. Severe fatty change and mild inflammation and necrosis occurred in C57 mice that received 150-mu-g TCDD/kg. In contrast, DBA mice exposed to 30-mu-g TCDD/kg developed hepatocellular necrosis and inflammation without any fatty change. Only slight hepatic lipid accumulation occurred with some necrosis and inflammation in DBA mice given 600-mu-g TCDD/kg. The Ah locus may play a role in determining the sensitivity of C57 mice to the steatotic effects of TCDD.