Effect of ethanol on cell growth and cholesterol metabolism in cultured Hep G2 cells.
The Hep G2 human hepatoma cell line has been recognized as an excellent in vitro human model system. For this reason, this line was used to study the effect of ethanol on HMG-CoA reductase activity concerning cell growth and cholesterol metabolism. Cells were incubated in ethanol-containing medium (0-400 mmol/L) for up to 102 h. Ethanol caused an inhibition in the growth rate and in HMG-CoA reductase activity that could be reverted by the removal of ethanol from the culture medium, indicating no cellular damage. These changes cannot be ascribed to the regulatory effect of cholesterol levels, since its content was not modified either in the cells or in the medium. The addition of mevalonate to the culture medium could not revert the growth rate inhibition evoked by ethanol. Moreover, ethanol produced an increment in the cholesterol efflux in [3H]cholesterol-prelabeled cells. We conclude that the decrease in HMG-CoA reductase activity evoked by ethanol treatment on Hep G2 cells would not be the cause but the consequence of the impairment in cellular growth, since this impairment could not be reverted by the addition of mevalonate to the culture medium.
Polo
Mónica P
MP
Instituto de Investigacions Bioquímicas de La Plata, CONICET-UNLP, Facultad de Ciencias Medicas, 1900 La Plata, Argentina.
de Bravo
Margarita G
MG
de Alaniz
María J T
MJ
D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D007553:Isotope Labeling; D008113:Liver Neoplasms / Q000201:enzymology* / Q000473:pathology; D008798:Mevalonic Acid / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D000431:Ethanol; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D008798:Mevalonic Acid