Interaction of cis-diamminedichloroplatinum(II) with sensitive and resistant L1210 cell lines. Drug binding to nuclei and DNA.
We used in parallel, to study the kinetics of cis-DDP cellular binding and distribution, a cL cell culture line established from L1210 murine leukemia ascites and its cLP derivative which acquired a 30-fold (ID50) resistance to cis-diamminedichloroplatinum(II). Cell cultures were incubated with 0.9 microgram/ml (3 microM) of the drug and after various incubation times up to 24 hr, the amount of platinum associated to whole cells, to isolated nuclei and to purified DNA was determined using atomic absorption spectrophotometry. For the first hours of incubation no significant difference in the rate of platinum association was observed between the two cell lines. After the first hours of incubation the amount of platinum associated to whole cells and to isolated nuclei was significantly higher in the drug sensitive cells. However, the rates of platinum association to the respective DNAs were quite similar in the two cell lines. Our study failed to demonstrate any significant quantitative modification of the overall drug-DNA association between the resistant and sensitive cell lines.
Laboratoire de Biochimie-Enzymologie (CNRS UA 147, INSERM U 140) Institut Gustave Roussy, Villejuif, France.
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M
Foka
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Belehradek
J
J
Paoletti
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D002945:Cisplatin / Q000378:metabolism* / Q000494:pharmacology; D004247:DNA / Q000378:metabolism*; D004351:Drug Resistance; D007939:Leukemia L1210 / Q000378:metabolism*; D051379:Mice; D008811:Mice, Inbred DBA; D010984:Platinum / Q000378:metabolism; D014407:Tumor Cells, Cultured
D010984:Platinum; D004247:DNA; D002945:Cisplatin