To analyze the role of the glutathione system in the cellular cadmium response, mouse embryonic fibroblasts with and without functional Mtf1 were treated with cadmium in combination with BSO, a specific inhibitor of glutamate-cysteine ligase (31), and cell viability was assessed by a colorimetric assay based on the tetrazolium salt MTT (Figure 6). Increasing concentrations of BSO or cadmium alone were to some extent cytotoxic for the examined cell lines. Treatment with both BSO and cadmium resulted in an enhanced lethality particularly for the cells without functional Mtf1, indicating that a depletion of glutathione together with a lack of Mtf1 impair an efficient anti-cadmium defense. Thus, adequate glutathione supply as well as MTF-1 and its target genes are essential for the survival of the cell under cadmium stress.