METALLOTHIONEIN EXPRESSION AND RESISTANCE TO CISPLATIN IN A HUMAN GERM-CELL TUMOR-CELL LINE

Expression of intracellular metallothionein (MT) has been linked to ci s-diamminedichloroplatinum (cDDP) resistance in human germ cell tumor cell lines. To determine whether exposure to cDDP would select for cel ls with increased MT expression, the MT content of the human teratocar cinoma cell line T7800 was measured after development of resistance to cDDP by exposure to progressively higher drug concentrations (6.25-25 mu M). cDDP-resistant cells (T7800R) had significantly higher MT mRNA and MT protein, increased resistance to killing by cDDP and altered i n vitro growth kinetics compared to parental T7800 cells. cDDP resista nce in a variety of other human tumor cell lines correlated with MT co ntent, with no significant difference in glutathione level. These data indicate that selection in vitro for cDDP resistance in human germ ce ll tumors coselects for cells with enhanced MT content. However, selec ted cells differed in characteristics other than MT content. They had a slower growth rate and, although the rank order of MT level in T7800 , T7800R and other human tumor cell lines correlated very well with cD DP resistance, differences in the level of MT expression did not corre spond with differences in the absolute level of cDDP resistance. These results suggest that increased MT expression is concomitant with incr eased cDDP resistance in a variety of human tumor cell lines. However, measured differences in MT levels may not accurately reflect the degr ee of cDDP resistance differences among those cells.