EFFECTS OF THE NATURALLY-OCCURRING FOOD MYCOTOXIN OCHRATOXIN-A ON BRAIN-CELLS IN CULTURE

The potential of ochratoxin A (OTA) to damage brain cells was studied by using a three-dimensional cell culture system as model for the deve loping brain. Aggregating cell cultures of foetal rat telencephalon we re tested either during an early developmental period, or during a pha se of advanced maturation, over a wide range of OTA concentrations (0. 4 nM to 50 mu M). By monitoring changes in activities of cell type-spe cific enzymes (ChAt and GAD, for cholinergic and GABAergic neurones, r espectively, GS for astrocytes and CNP for oligodendrocytes), the conc entration-dependent toxicity and neurodevelopmental effects of OTA wer e determined OTA proved to be highly toxic, since a 10-day treatment a t 50 nM caused a general cytotoxicity in both mature and immature cult ures. At 10 nM of OTA, cell type-specific effects were observed : in i mmature cultures, a loss in neuronal and oligodendroglial enzyme activ ities, and an increase in the activity of the astroglial marker glutam ine synthetase were found. Furthermore, at 2 and 10 nM of OTA, a clust ering of microglial cells was observed. In mature cultures, OTA was so mewhat less potent, but caused a similar pattern of toxic effects. A 2 4 h-treatment with OTA resulted in a concentration-dependent decrease in protein synthesis, with IC50 values of 25 nM and 33 nM for immature and mature cultures respectively. Acute (24 h) treatment at high OTA concentrations (10 to 50 mu M) caused a significant increase in reacti ve oxygen species formation, as measured by the intracellular oxidatio n of 2',7'-dichloroflourescin. These results suggest that OTA has the potential to be a potent toxicant to brain cells, and that its effects at nanomolar concentrations are primarily due to the inhibition of pr otein synthesis, whereas ROS seem not to be involved in the toxicity m ediated by a chronic exposure to OTA at such low concentrations. (C) I ntox Press, Inc. 1997.