Zm. Szczepiorkowski et al., FATTY-ACID ETHYL-ESTERS DECREASE HUMAN HEPATOBLASTOMA CELL-PROLIFERATION AND PROTEIN-SYNTHESIS, Gastroenterology, 108(2), 1995, pp. 515-522
Background/Aims: Fatty acid ethyl esters (FAEEs) are nonoxidative prod
ucts of ethanol metabolism. They have been implicated as mediators of
ethanol-induced organ damage because FAEE and FAEE synthase have been
found specifically in the organs damaged by ethanol abuse. This study
showed toxicity specifically related to FAEE or their metabolites for
intact human hepatoblastoma-derived cells (HepG2). Methods: The lipid
core of human low-density lipoprotein (LDL) was extracted and the LDL
particle reconstituted with either ethyl oleate or ethyl arachidonate.
Cultured HepG2 cells were incubated with LDL containing FAEE. Cell pr
oliferation was measured by [methyl-H-3]thymidine incorporation. Prote
in synthesis was determined using L-[S-35]methionine. Results: Incubat
ion of cells with 600 mu mol/L ethyl oleate or 800 mu mol/L ethyl arac
hidonate decreased [methyl-H-3]thymidine incorporation into HepG2 cell
s by 31% and 37%, respectively. LDL reconstituted with 400 mu mol/L et
hyl oleate decreased protein synthesis in intact HepG2 cells by 41%. E
lectron microscopy revealed significant changes in cell morphology, pa
rticularly involving the cell nucleus. FAEE delivered in reconstituted
LDL were rapidly hydrolyzed and the fatty acids re-esterified into ph
ospholipids, triglycerides, and cholesterol esters, with preference fo
r triglycerides. Conclusions: These findings provide evidence that FAE
E are toxic for intact human hepatoblastoma cells and that they or the
ir metabolites may be an important causative agent in ethanol-induced
liver damage.