Actions of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the human hepatoblastoma HEPG 2 tissue culture cell line: Functional and electron microscopic observations

Abstract

The HepG 2 tissue culture cell line was derived from a human hepatoblastoma and has maintained hepatocyte functions such as the synthesis of albumin. We studied the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on enzyme induction and ultrastructure of HepG 2 cells. TCDD (1 nM) caused a 40-fold induction of aryl hydrocarbon hydroxylase activity. HepG 2 cytosolic fractions (1) contain saturable binding site for TCDD. Because alterations in the ultrastructure of the liver have been associated with exposure of humans and laboratory animals to TCDD and other halogenated polycyclic aromatic compounds, we examined the effects of TCDD on morphology of HepG 2 cells. Unexpectedly, both control and TCDD-treated (30 nM for 7 days) HepG 2 cells showed similar morphology as determined by electron microscopy. The cells contained extensive rough endoplasmic reticulum and free ribosomes; mitochondria and nuclei were similar in control and treated cells. In contrast to previous studies with rats and mouse hepatoma cells (Hepa-1) in tissue culture, HepG 2 cells showed no increased accumulation of lipid droplets or endoplasmic reticulum and no mitochondrial alterations in TCDD-treated cells. Based on the current finding of minimal morphological effects of TCDD on this cell culture line, it is interesting to speculate that the morphological alterations observed in human or rodent liver following in vivo exposure may represent indirect effects of TCDD or may involve genes that are not expressed in HepG 2 cells.