Differential uptake of cis-diamminedichloroplatinum (II) by sensitive and resistant murine L1210 leukemia cells.
The uptake of cis-[14C]dichloro(ethylenediamine)platinum(II) (cis-DEP) is reduced in cis-diamminedichloroplatinum(II) (cis-DDP)-resistant L1210 cells [L1210/DDP (SRI)] in comparison to cis-DDP-sensitive L1210 cells (L1210/0). A difference in uptake is observed as early as 6 min after addition of cis-[14C]DEP and increases to approximately 3-fold after 30 min. This reduction in uptake is reflected in a decrease in the binding of platinum to DNA isolated from cis-DDP-treated cells as measured by atomic absorption spectroscopy and in the quantity of intracellular cis-DEP metabolites as measured by high-performance liquid chromatography. Similar differences in uptake are observed between ascitic L1210/0 and L1210/DDP (SRI) cells in vitro and in vivo, showing that the differences in uptake are not due to an artifact of the culturing process. The differences in cis-DEP uptake between the two cell lines were relatively unchanged during 7 mo in culture; however, both cell lines exhibited altered sensitivities to cis-DEP during extended culturing. No difference was observed in the efflux of cis-DEP by the two cell lines. Similarly, no difference in nonprotein and total sulfhydryl contents was observed between L1210/0 and L1210/DDP (SRI) cells. The difference in uptake (3-fold) of cis-DEP between L1210/0 and L1210/DDP (SRI) cells may not account fully for the observed differences in sensitivity of the two cell lines to cis-DDP (18-fold) and cis-DEP (19-fold). A portion of the resistance may be due to differences in the capacity of the two cell lines to survive in the presence of platinum damage.
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Kettering-Meyer Laboratory, Southern Research Institute, Birmingham, Alabama 35255.
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002945:Cisplatin / Q000493:pharmacokinetics*; D004247:DNA / Q000378:metabolism; D004351:Drug Resistance; D007939:Leukemia L1210 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010984:Platinum / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D010984:Platinum; D004247:DNA; D002945:Cisplatin