ENRICHMENT FOR METALLOTHIONEIN DOES NOT CONFER RESISTANCE TO CISPLATIN IN TRANSFECTED NIH 3T3 CELLS/

Evidence has been presented both that metallothionein does and does no t produce resistance to cisplatin. The metallothionein-enriched cells described in most previous studies have been selected for resistance t o heavy metals, such as cadmium, or have been maintained in a medium e nriched for the metals. Exposure to toxic metals could alter the cells in many ways. This report addresses the effect of metallothionein con tent alone, independent of exposure to metals, on cellular resistance to cisplatin. The toxicity of cisplatin was compared in NIH/3T3 cells that vary in their content of metallothionein as a consequence of tran sfection with a plasmid that results in the constitutive expression of metallothionein. The plasmid contains the bovine papillomavirus genom e and the mouse metallothionein-I gene; it is driven by a glucose-regu lated protein of 78 kD. Control cells were transfected with a similar plasmid in which the coding sequences for metallothionein were inverte d and separated from the promoter, thereby abolishing expression. Expr ession of metallothionein required neither selection nor maintenance o f cells in the presence of heavy metals. Despite large differences bet ween the two types of cells in their cellular content of metallothione in and in their resistance to the toxicity of cadmium, no differences in resistance to cisplatin were observed.