Clonal response to ethanol of proliferating rat hepatoma cells in vitro

We have grown HTC cells (ascites variant of Morris hepatoma 7288c) in spinner cultures in the presence of various concentrations of ethanol, both in short-term incubations and in chronically exposed cultures. In short-term exposures cell proliferation is decreased in a dose-related fashion, falling to approximately 25% of control values at 35 mM ethanol. In refed cultures maintained at ethanol concentrations gradually increased to 17 mM, there is an initial decrease in proliferation followed by stabilization. Comparison of the growth patterns of cells chronically exposed to ethanol with the growth patterns of uncloned naive cells suggests the presence of both ethanol-sensitive and -resistant HTC cell clones. Preliminary cloning experiments have been successful in demonstrating that HTC clones do exist which have widely varying responses to ethanol. Clones have been isolated which are growth-inhibited by low concentrations of ethanol whereas others are resistant or even stimulated in the same concentration range. The critical differences between ethanol-sensitive and -resistant HTC cells are currently unknown, but the general phenomenon of clonal selection during chronic ethanol exposure is of interest in the pathogenesis of alcohol-related diseases.