BIOTRANSFORMATION OF CARBON-TETRACHLORIDE IN CULTURED NEURONS AND ASTROCYTES

The ability of brain neuronal cells to metabolize carbon tetrachloride (CCl4,) has been studied in an attempt to explain earlier observed to xic effects of CCl4 on these cells. The expression of cytochrome P-450 , the glutathione (GSH) content and the activity of glutathione-S-tran sferase (GST) were measured in cultured neurons and astrocytes from ch ick embryo cerebral hemispheres. The metabolism of CCl4 in the neuron and astrocyte cultures was also assessed by determining the formation of:CCl2, in membrane preparations of these cells. In the membrane frac tions of neurons and astrocytes, no measurable levels of cytochrome P- 450 were observed. Nevertheless, neurons as well as astrocytes had a c apacity for the metabolism of CCl4. The metabolic capacity of the neur ons was significantly greater than that of the astrocytes. The neuron cultures had a higher initial content of GSH and a higher control acti vity of GST than had the astrocytes. Neither the GSH level nor GST act ivity were significantly affected in the neuron cultures after exposur e to CCl4. In astrocyte cultures 2 mM CCl4, slightly depleted the GSH level and significantly induced GST activity. At 3 mM CCl4, GSH was de pleted by 30% and by more than 50% at 4 mM CCl4 It Can be concluded th at the metabolic activation of CCl4, was higher in neurons than in ast rocytes. This can explain the earlier observation of CCl4-induced lipi d peroxidation in cultured neurons. Moreover, neuron GSH was not able to protect these cells against CCl4,-induced peroxidative damage. In t he astrocytes, on the other hand, GSH and GST appeared to have a role in detoxification of CCl4.