Effects of Ethanol and Basic Fibroblast Growth Factor on the Transforming Growth Factor β1 Regulated Proliferation of Cortical Astrocytes and C6 Astrocytoma Cells

Abstract

The effects of ethanol on transforming growth factor beta1 (TGFbeta1)-regulated proliferation of primary cultured cortical astrocytes and C6 astrocytoma cells were determined. Cultured cells were treated with TGFbeta1 (0 or 10 ng/ml) and ethanol (0 or 400 mg/dl) for as many as 4 days. The effects of these treatments on cell growth (the change in cell number) and cell proliferation (incorporation of [3H]thymidine) were determined. In addition, the effects of serum and basic fibroblast growth factor (bFGF) on TGFbeta1-affected cell proliferation were examined. Both TGFbeta1 and ethanol inhibited cell growth and proliferation among the two types of cells; this effect was only evident when the cells were grown in the presence of a mitogen, serum, or bFGF. When added together (either in a serum-supplemented or serum-free medium), however, TGFbeta1 and the mitogen effectively nullified each other. TGFbeta1 blocked the mitogenic effect of bFGF on astrocytes and C6 cells. Ethanol did not affect (i.e., neither added nor nullified) this antagonistic effect. TGFbeta1, like ethanol, is a potent anti-proliferative agent; either can nullify the mitogenic activity of serum or bFGF. Astrocytes and astrocyte-like cells react to combined TGFbeta1 and ethanol treatment differently than do neurons for which the inhibitory effects of TGFbeta1 and ethanol are additive.