Effects of ochratoxin A on cytotoxicity and cell differentiation in cultured rat embryonic cells

In the present study, the effects of ochratoxin A (OTA) on cytotoxicity, ce ll differentiation, and other cell functions in the embryonic midbrain cell s, which are dopaminergic, were compared to those in the limb bud cells, wh ich are nondopaminergic, to assess the selectivity of OTA central action. T welve-day rat embryo midbrain and limb bud cells were cultured in Dulbecco' s modified Eagle's medium nutrient and Ham's F12 (1:1) mixture containing 1 0% Nuserum for 96 h in the presence of various concentrations of OTA. OTA s ignificantly reduced the levels of protein, DNA and glutathione, and [H-3] thymidine incorporation into DNA in both embryonic midbrain and limb bud ce lls in a similar concentration-dependent manner. The IC50 values for cytoto xicity measured by neutral red uptake were 1.10 muM in the midbrain cells a nd 1.05 muM in the limb bud cells. The IC50 values of cell differentiation were 1.10 muM in the midbrain cells and 1.0 muM in the limb bud cells. The addition of exogenous glutathione (32.5 muM) did not change the OTA-induced fall in protein and DNA levels, or the IC50 values of cytotoxicity and dif ferentiation in the midbrain and limb bud cells. Data show that OTA does no t appear to exert a selective toxic dopaminergic cell action and that OTA-i nduced cytotoxicity and inhibition of cell differentiation were not prevent ed by exogenous glutathione.