Responses in astrocytic C6 glioma cells to ethanol and dibutyryl cyclic AMP

Late passage C-6 glioma cells exhibit astrocytic properties as shown by a characteristic cell morphology and by high levels of the astrocytic cell maker glutamine synthetase (GS). In this study the effects of ethanol (0.2%-1.0% w/v) on the pattern of dibutyryl cyclic AMP (dBcAMP, 1 mM)-induced differentiation were examined using cell number and DNA content as indices for proliferation and cell morphology and GS activity to evaluate differentiation. Differences were observed in the susceptibility of cells to dBcAMP alone, ethanol alone, or simultaneous exposure to both drugs, when cultures were compared at logarithmic and postconfluent phases of growth. Exposure to dBcAMP decreased cell proliferation, induced a characteristic change in cell shape and increased GS activity. In logarithmic phase, simultaneous exposure of cells to ethanol and dBcAMP delayed the dBcAMP-induced change in cell shape and attenuated the mitosis-restricting properties of exposure to dBcAMP. Furthermore, GS activity was greater in dually treated cultures than in cultures treated with dBcAMP alone. We interpret this higher enzyme activity to be the consequence of increased cell-cell contact resulting from larger numbers of cells in the dually treated cultures, coupled with a subsequent dBcAMP-induction of this cytosolic enzyme. In postconfluent cultures, ethanol-exposure did not statistically alter DNA content; whereas GS activity was lower, suggesting that synthesis of GS may be impaired by cellular exposure to ethanol. Furthermore, enzyme activity was also lower in cultures treated with dBcAMP in concert with ethanol than in those treated with dBcAMP alone.(ABSTRACT TRUNCATED AT 250 WORDS)