THE INFLUENCE OF GLUTATHIONE ON THE CYTOTOXICITY OF METALS IN RAT HEPATOMA-DERIVED FA32 CELLS

The cytotoxicities of mercury, cadmium, nickel, cobalt, zinc and coppe r were investigated in rat hepatoma-derived Fa32 cells by using the ne utral red uptake inhibition assay with three treatment regimens (2 hou rs, 24 hours and 1 week). Nickel and cobalt were almost non-toxic afte r 2 hours. Good correlations were observed between the 24-hour and the 1-week cytotoxicities, and cytotoxicity in human hepatoma-derived Hep G2 cells. L-buthionine-S,R-sulphoximine reduced the glutathione conte nt to 5% after 24 hours. The cytotoxicity of the metals increased (3-1 2 times) in glutathione-depleted cells. A good agreement was demonstra ted by HPLC between the glutathione S-transferase (GST) subunit compos ition in Fa32 cells and in rat liver, except that subunit 7 is also a major subunit in the hepatoma cell line. No evidence was obtained for an interaction of the GSTs in the glutathione-modulated cytotoxicity o f the investigated metals.