Ethanol neurotoxicity. 1. Direct effects on replicating astrocytes.

Abstract

Experiments were conducted to investigate the direct effects of ethanol on the DNA, RNA and protein content of rapidly growing astroglia. Astrocyte progenitor cells obtained from the neopallia of newborn mice were grown for 6 days in primary culture and then exposed continuously to ethanol (0.0, 0.06, 0.12 or 0.24 g/dl) for 11 days. The in vitro exposure period corresponds to the period of peak astroglial replication and growth in the mouse brain growth spurt in situ (postnatal days 6 to 17). DNA, RNA and protein contents were all significantly different in ethanol-exposed astroglial cultures compared to controls (p less than 0.0005) and there was an unexpected, but highly consistent, concentration-related pattern to this effect, namely, an increased content relative to controls at the lowest ethanol concentration, and a progressive decrease in content with increasing ethanol concentrations. Our data indicate that different cell processes contributing to growth are more vulnerable to ethanol's toxicity than others. RNA and protein contents are reduced to a greater degree and at lower ethanol concentrations than is DNA content. The "growth-promoting" effect seen in these in vitro studies emphasizes the fact that factors which are secondary to alcohol consumption contribute significantly to the alcohol-related brain growth deficits which are seen in vivo. Ethanol acting alone appears to exert a "growth-impairing" effect only at high concentrations.