ETHANOL INCREASES APOLIPOPROTEIN-B MESSENGER-RNA EDITING IN RAT PRIMARY HEPATOCYTES AND MCARDLE CELLS

Apolipoprotein B (apoB) mRNA editing involves a site-specific cytidine to uridine transition catalyzed by the cytidine deaminase, APOBEC-1, in the context of and regulated by a multi-protein-containing editosom e. ApoB mRNA editing in vivo is subject to tissue specific, developmen tal and metabolic regulation. me demonstrate for the first time that t he amount of edited apoB mRNA in rat primary hepatocytes is markedly i ncreased subsequent to transient treatment with ethanol in vitro. The apparent change in editing efficiency was dosedependent (from 0.1%-2.4 % initial ethanol dose) and occurred with rapid onset. The proportion of edited apoB mRNA was also markedly enhanced in a rat hepatoma cell line, McArdle RH7777 cells and in a stable McArdle cell Line over-expr essing APOBEC-1 by transient treatment with 2.5 % ethanol. in contrast , the apoB mRNA editing in a human hepatoma cell line, HepG2 cells and a stable HepG2 cell line over-expressing APOBEC-1 did not respond to ethanol treatment. The data support the possibility that editing activ ity is ethanol-responsive but suggest that this change is cell type-sp ecific. (C) 1998 Academic Press.