MODULATION OF LIVER-SPECIFIC CELLULAR-RESPONSE TO ETHANOL IN-VITRO INHEP G2 CELLS

The aim of this study was to investigate in vitro in a human hepatobla stoma cell line, Hep G2, the effect of ethanol (EtOH) toxicity. The ul trastructural changes were assessed by performing quantitative light a nd transmission electron microscopy. The second objective of this stud y was to define further EtOH-induced biochemical changes associated wi th mitochondrial function. In comparison with controls, after exposure to 80 mM EtOH cells showed: a threefold increase in length of mitocho ndria; proliferation, vesiculation and dilatation of smooth endoplasmi c reticulum, and twofold increases in the size of lipid droplets and i n their number/cell. Exposure of cells to two doses of EtOH augmented the ultrastructural alterations observed after a single dose. Cytoviab ility, assessed by metabolism of methylxanthine dye decreased signific antly by (P < 0.0001) to 68% of the control after one dose and was fur ther reduced after the second dose of EtOH (P < 0.001). Succinate dehy drogenase activity in cells treated for 24 hr with 80 mM EtOH was decr eased to about 80% of control values after one 24-hr treatment with 80 mM EtOH and to about 55% of control values after two 24-hr exposures. This in vitro model of ethanol-induced cytotoxicity in Hep G2 cells i s able to reproduce essential ultrastructural features of alcohol-rela ted hepatitis, in humans, including steatosis and dose-dependent hepat ocytotoxicity. The present work represents the first morphometric stud y to measure changes produced by EtOH exposure in human-derived liver cells. (C) 1998 Elsevier Science Lad. All rights reserved.