Cross-resistance between cisplatin, antimony potassium tartrate, and arsenite in human tumor cells.
Cross-resistance between cisplatin (DDP) and metalloid salts in human cells was sought on the basis that mechanisms that mediate metalloid salt cross-resistance in prokaryotes are evolutionarily conserved. Two ovarian and two head and neck carcinoma cell lines selected for DDP resistance were found to be cross-resistant to antimony potassium tartrate, which contains trivalent antimony. The DDP-resistant variant 2008/A was also cross-resistant to arsenite but not to stibogluconate, which contains pentavalent antimony. A variant selected for resistance to antimony potassium tartrate was cross-resistant to DDP and arsenite. Resistance to antimony potassium tartrate and arsenite was of a similar magnitude (3-7-fold), whereas the level of resistance to DDP was greater (17-fold), irrespective of whether the cells were selected by exposure to DDP or to antimony potassium tartrate. In the resistant sublines, uptake of [3H]-dichloro(ethylenediamine) platinum(II) was reduced to 41-52% of control, and a similar deficit was observed in the accumulation of arsenite. We conclude that DDP, antimony potassium tartrate, and arsenite all share a common mechanism of resistance in human cells and that this is due in part to an accumulation defect.
Naredi
P
P
Department of Surgery, Sahlgrenska University Hospital, Göteborg, Sweden.
Heath
D D
DD
Enns
R E
RE
Howell
S B
SB
D000838:Anions / Q000494:pharmacology; D000966:Antimony Potassium Tartrate / Q000494:pharmacology* / Q000633:toxicity; D018053:Arsenites / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D001692:Biological Transport; D002277:Carcinoma; D002945:Cisplatin / Q000494:pharmacology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple / Q000502:physiology*; D005260:Female; D006258:Head and Neck Neoplasms; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000378:metabolism / Q000494:pharmacology; D010051:Ovarian Neoplasms; D012641:Selection, Genetic; D014407:Tumor Cells, Cultured
D000838:Anions; D018053:Arsenites; D009944:Organoplatinum Compounds; C002892:platinum ethylenediamine dichloride; D000966:Antimony Potassium Tartrate; C015001:arsenite; D002945:Cisplatin