The interaction of platinum and anthrapyrazole antitumor drugs with mouse thymocytes studied by terbium fluorescence

Abstract

The fluorescent lanthanide, terbium has been employed to study the effect of a series of platinum and anthracycline drugs and an anthrapyrazole (oxanthrazole) on terbium binding to mouse thymocytes. It was observed that terbium fluorescence intensity was markedly decreased by two platinum drugs (cis-dichlorodiammine platinum(II) (cis-DDP) and cis-dichloro-trans-dihydroxybis(isopropylammine) platinum(IV) (CHIP)) and an anthrapyrazole (oxanthrazole), but that the lipophylic derivative cis-diammine-1,1-cyclobutanedicarboxylate platinum(II) had a small but significant effect and the anthracyclines (at low concentrations) had no effect. The calcium channel blocker, verapamil also had no effect. The effect of cis-DDP was markedly dependent on ionic strength in contradistinction to CHIP. The decreases in phosphorescence decay produced by cis-DDP also showed a marked dependence on ionic strength. It is proposed that cis-DDP interacts with the membrane primarily by a charge effect, but that CHIP may produce a conformational change in the membrane. These data are interesting, since the lipophylic platinum drugs (CHIP and CBDCA) also increased significantly the amount of bound intracellular calcium, but all the drugs decreased mitogen-stimulated calcium uptake into mouse thymocytes.