Several genes involved in the metabolism of the antioxidant glutathione were found to be upregulated by cadmium exposure, namely the genes encoding the catalytic subunit of glutamate-cysteine ligase (Gclc) that is the rate limiting enzyme in de novo synthesis of glutathione (45); glutathione reductase 1 (Gsr), the reducing enzyme for oxidized glutathione (45); and glutathione-S-transferase, mu 4 (Gstm4), which is a member of the glutathione-S-transferase supergene family of detoxification enzymes (45). In all of these cases, induction was confirmed by semiquantitative RT–PCRs (data not shown). Gclc, also referred to as heavy chain subunit of gamma-glutamylcysteine synthetase (Ggcs-hc), had been discussed previously as a target gene of MTF-1 (6). Our expression data indicate that Gclc is induced by cadmium but, at least in the adult mouse liver, not dependent on MTF-1.