Induction of metallothionein is correlated with resistance to auranofin, a gold compound, in Chinese hamster ovary cells.
Metallothioneins (MTs) are low molecular weight, thiol-rich, metal-binding proteins. Auranofin (AF) is a gold compound active in the treatment of rheumatoid arthritis. The effects of AF on regulation of MT gene expression in Chinese hamster ovary cells were studied. AF-resistant cells accumulated substantial amounts of MT mRNA and protein, whereas no induction was observed in AF-sensitive cells. Cells capable of inducing MT in the presence of AF were much less sensitive to AF-mediated cytotoxicity. Induction of MT by low concentrations of Cd protected cells from subsequently administered doses of AF. The level of protection correlated with the level of induced MT. These findings indicate that MT plays a central role in the mechanisms underlying cellular resistance to gold compounds.
D000818:Animals; D001310:Auranofin / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000633:toxicity; D002104:Cadmium / Q000494:pharmacology / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D004351:Drug Resistance; D005786:Gene Expression Regulation / Q000187:drug effects; D008668:Metallothionein / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics
D012333:RNA, Messenger; D002104:Cadmium; D001310:Auranofin; D008668:Metallothionein