ATLA::Alternatives to Laboratory Animals

Volume 24, Number 3

The influence of glutathione on the cytotoxicity of metals in rat hepatoma-derived Fa32 cells.

ATLA 24, 399-403, May/June 1996

Paul J. Dierickx

Instituut voor Hygiëne en Epidemiologie, Afdeling Toxikologie, Wytsmanstroat 14, 1050 Brussels, Belgium

SUMMARY

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 nontoxic after 2 hours. Good correlations were observed between the 24-hour and the 1-week cytotoxicities, and cytotoxicity in human hepatomaderived 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