INFUSION OF BILE FROM METHYLENE DIANILINE-TREATED RATS INTO THE COMMON BILE-DUCT INJURES BILIARY EPITHELIAL-CELLS OF RECIPIENT RATS

Methylene dianiline (4,4'-diaminodiphenylmethane, DAPM) rapidly causes cholestasis and injury to biliary epithelial cells (BEG) in the liver and common bile duct of rats. Our objective was to determine if the p roximate toxicant(s) was present in bile. Bile from DAPM-treated or co ntrol rats was infused through the common bile duct of untreated rats via inflow and outflow cannulas for 4 h. Cholestasis, increases in ser um constituents, and intrahepatic BEC injury in the livers of DAPM-tre ated donor rats at 4 h were comparable to previous studies (Kanz et al ., Toxicol. Appl. Pharmacol. 117 (1992) 88-97) [1]. BEC injury in the common bile duct of rats receiving DAPM bile or control bile was asses sed by point counting. Percent necrosis was > 28% in the common bile d uct of rats receiving DAPM bile compared to < 5% in rats receiving con trol bile. These results indicate that bile is a major route of BEC ex posure to DAPM proximate toxicant(s) and demonstrate the utility of a new method for investigating mechanisms of biliary toxicants.