Regulation of metallothionein gene expression in mammalian cells by gold compounds.

Metallothioneins are a class of low molecular weight, cysteine-rich proteins. Metallothioneins bind heavy metals and are thought to play a role in metal metabolism. Auranofin, an antiarthritic gold compound, is a potent inducer of metallothionein in Chinese hamster ovary cells. The induction of metallothionein by auranofin was mediated by active transcription of the gene and new mRNA was accumulated within 30 min after the exposure of Chinese hamster ovary cells to the drug. The extent of metallothionein induction was related to the concentration of the compound and was affected by the nature of the ligand attached to the gold molecule. A subline of these Chinese hamster ovary cells was established by growing them in the presence of normally cytotoxic concentrations of auranofin. In this auranofin-resistant cell line, the metallothionein genes were actively transcribed in the presence of auranofin, suggesting a relationship between cytotoxic action of auranofin and metallothionein gene transcription. Regulation of metallothionein gene transcription may play an important role in the molecular mechanism(s) of action auranofin and resistance to it.