3,4,3,4'-Tetrachlorobiphenyl-Induced Effects in the Rat Liver. II. Electron Microscopic Autoradiographic Localization of H-TCB

Abstract

Recent results (3) indicate that 200 mg 3,4,3′,4′-tetrachlorobiphenyl induces hepatomegaly accompanied by significant decreases in serum and hepatic retinoid content and hepatocyte morphologic alterations of proliferated and vesiculated endoplasmic reticulum and megamitochondria with paracrystalline inclusions. There was also an associated change in the number, size, and distribution of lipid droplets in hepatocytes and fat-storing cells. Electron microscopic autoradiographic techniques were utilized to determine the cellular and subcellular distribution of 3H-3,4,3′,4′-tetrachlorobiphenyl (3H-TCB) in the adult rat liver and determine if there is any relationship between subcellular morphologic change and radiolabel localization. Adult female WAG/Rij rats received a single intraperitoneal injection of 200 mg TCB/kg containing 1.85 mCi of 3H-TCB and were sacrificed at 1, 3, 7, and 14 days following exposure. The vast majority of 3H-TCB-derived radioactivity was located in the hepatocyte at all time points examined, ranging from 79–86% of the total number of autoradiographic grains counted over the liver cells. Sequential order of radiolabel localization per liver cell type at 1, 3, and 7 days was hepatocyte > > > Kupffer cell > fat-storing cell > endothelial cell. At day 14, the sequential order of radiolabel localization per liver cell type was hepatocyte > > > fat-storing cell > Kupffer cell > endothelial cell, which indicates that there was some shift movement of label over time. The lipid droplet, mitochondria, and endoplasmic reticulum were the subcellular structures or organelles of hepatocytes having the highest number of 3H-TCB-derived grains at all time periods examined. The predominant morphological alterations induced following TCB intoxication were observed in these organelles. The results of this study suggests that there is an association between TCB localization and morphologic change induced in mitochondria and endoplasmic reticulum of hepatocytes following TCB exposure.