Comparison of 2, 3, 7, 8-tetrachlorodibenzo-p-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/6] (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 hydro-carbon hydroxylase (AHH) activity (3 pg/kg for C57 and 30 pg/kg for DBA mice) and at doses approaching the LD50 (150 pg/kg for C57 and 600 pg/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 pg 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 pg TCDD/kg. In contrast, DBA mice exposed to 30 pg 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 pg TCDD/kg. The Ah locus may play a role in determining the sensitivity of C57 mice to the steatotic effects of TCDD.