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 s alt cross-resistance in prokaryotes are evolutionarily conserved. Two ovarian and two head and neck carcinoma cell lines selected for DDP re sistance were found to be cross-resistant to antimony potassium tartra te, which contains trivalent antimony. The DDP-resistant variant 2008/ A was also cross-resistant to arsenite but not to stibogluconate, whic h contains pentavalent antimony. A variant selected for resistance to antimony potassium tartrate was cross-resistant to DDP and arsenite. R esistance to antimony potassium tartrate and arsenite was of a similar magnitude (3-7-fold), whereas the level of resistance to DDP was grea ter (17-fold), irrespective of whether tire cells were selected by exp osure to DDP or to antimony potassium tartrate. In the resistant subli nes, uptake of [H-3]-dichloro(ethylenediamine) platinum(II) was reduce d to 41-52% of control, and a similar deficit was observed in the accu mulation of arsenite. We conclude that DDP, antimony potassium tartrat e, and arsenite all share a common mechanism of resistance in human ce lls and that this is due in part to an accumulation defect.