Cross-resistance to ouabain in a murine leukemia cell variant selected for cis-dichlorodiammineplatinum(II) resistance

A murine leukemic cell line (R1.1) variant (R1.1/CDDPR-E8) resistant to cis-dichlorodiammineplatinum(II)(CDDP) was also found to be resistant to ouabain, a postulated specific inhibitor of sodium-potassium ATPase. The variant established by the culture of parental cells in step by step increasing concentrations of CDDP, exhibited 11-fold higher resistance to CDDP than the parental R1.1 cells. The present study suggests that a mutational change leading to an alteration in cell membrane characteristics associated with ouabain has also changed the sensitivity of cells against CDDP. Alternatively, the present data may indicate that the cytotoxicity of CDDP is closely linked to its effects on cell membrane.