Glutathione restores normal cell activation and cell cycle progression in cis-platinum treated human lymphocytes

Abstract

Cis-platinum (CDDP) induces severe inhibition of cell activation and cell cycle progression in PHA-stimulated human PBL's. Applying the novel BrdU/Hoechst flow cytometric technique for high resolution cell cycle analysis we show that CDDP induced multiple cell kinetic disturbances occur simultaneously comprising G0/G1-arrest, and slow down and arrest of cells in S and G2/M-phase. We investigated whether the administration of reduced glutathione (GSH) might rescue cells from proliferative disturbances induced by CDDP. GSH at 0.15 mg ml-1 only partially restored normal cell activation and cell cycle progression. However, at 1.5 mg ml-1 a complete normal proliferation pattern was obtained. At the highest GSH dose rescue from inhibition of cell activation (G0/G1-phase arrest) as well as of cell cycle progression (S- and G2/M-phase arrest) was also present after delayed addition of GSH (1, 4 and 20 h) to CDDP treated PBL's. In addition cell viability of CDDP exposed PBL's is restored after GSH treatment. Our in vitro experiments give evidence that an increase of WBC found in CDDP/GSH treated patients has a real underlying cellular physiological mechanism protecting human peripheral lymphocytes from CDDP toxicity.