Ethanol induced growth inhibition and growth adaptation in vitro. Cell cycle delay in late G1.

We have characterized the growth responses of HTC rat hepatoma sublines after exposure to clinically relevant concentrations of ethanol. These experiments demonstrate growth inhibition by ethanol, and both adaptive and non-adaptive growth responses after chronic exposure. Examination of the cell cycle compartmentation of HTC lines shows that a rapid accumulation of G0/G1 cells is induced by ethanol. Estimates of cellular G1 RNA content by flow cytometry reveal increases in mean G1 RNA and in late G1 cells in the line which growth adapts, and decreases in these parameters in a line which does not adapt to ethanol. Both the growth responses and the timing of cell cycle restriction by ethanol in the adapting line suggest parallels with the reported data for regenerating rat liver. Ethanol induced late G1 restriction appears to be of significant interest in the study of cellular mechanisms which are disturbed by ethanol in proliferating tissues.