Amino acid membrane transport properties of L1210 cells resistant to cisplatin.

A mouse L1210 leukemia cell line was made 18-fold resistant to the chemotherapeutic agent cisplatin. The drug resistant cells exhibited changes in morphologic and biochemical properties from the sensitive cells. Uptake of labeled cisplatin was only slightly decreased in the resistant cells. However, the exogenous methionine requirement for these cells was 18-fold less than for parent cells. This decrease in the methionine requirement was also associated with differences in both methionine metabolism and transport. Membrane transport analysis revealed different Kt and Vmax properties for methionine and a nonmetabolizable amino acid analogue between the two cell lines. In L1210 cells resistant to cisplatin, decreases in amino acid transport, plus changes in amino acid substrate specificities, may be related to a drug-membrane phenomenon which could be one mechanism of resistance to chemotherapeutic agents.