The Influence of Glutathione on the Cytotoxicity of Metals in Rat Hepatoma-derived Fa32 Cells

Abstract

The cytotoxicities of mercury, cadmium, nickel, cobalt, zinc and copper were investigated in rat hepatoma-derived Fa32 cells by using the neutral red uptake inhibition assay with three treatment regimens (2 hours, 24 hours and 1 week). Nickel and cobalt were almost non-toxic after 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 content to 5% after 24 hours. The cytotoxicity of the metals increased (3–12 times) in glutathione-depleted cells. A good agreement was demonstrated by HPLC between the glutathione S-transferase (GST) subunit composition 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 of the investigated metals.

Keywords

neutral red mercury cadmium nickel cobalt zinc copper Fa32 cells glutathione glutathione S-transferase

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