[Flow cytometric analysis of the effect of DWA2114R on the cell cycle traverse of RPMI 8402 cells--comparison with CDDP]

Gan To Kagaku Ryoho. 1992 Apr;19(4):469-76.
[Article in Japanese]

Abstract

The (-) - (R) - 2-aminomethylpyrrolidine (1, 1-cyclobutanedicarboxylato) platinum(II) monohydrate, DW A2114R, is a new derivative of cis-dichlorodiammineplatinum(II), CDDP, which is reported to have a lower nephrotoxicity than CDDP. In this report, we investigated the effects of DW A2114R, in comparison with CDDP, on the cell growth, the cell cycle traverse and the colony-forming ability of human leukemia RPMI 8402 cells in vitro. The inhibitory effects of DW A2114R on the cell growth and the colony-forming ability were about 1/10 and 1/10-1/30, respectively, of the CDDP dose. And DW A2114R showed a higher time-dependency than CDDP in the experiment comparing exposure time to the drugs. Analysis of DNA histograms obtained by flow cytometry revealed that DW A2114R had a similar effect on the cell cycle traverse to that of CDDP. Both drugs exerted their growth-inhibitory effect by blocking cells at G2 phase. At higher concentrations, they prolonged the traverse of cells through S phase and completely inhibited them throughout the cell cycle. The comparative study on the colony-forming ability suggested that the G2 phase accumulation was irreversible and that these drugs are lethal, so the G2 phase accumulation could be considered a cytocidal effect of the drugs. In early clinical studies, however, the dose of DW A2114R was put at about 15-fold higher than the therapeutic dose of CDDP. This was comparable with our results in vitro and DW A2114R showed a much lower toxicities, with special regard to nephrotoxicity, than CD DP. These clinical data and our results suggest that DW A2114R could be clinically effective as an antitumor agent.

Publication types

  • Comparative Study
  • English Abstract

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Carboplatin / analogs & derivatives*
  • Carboplatin / pharmacology
  • Cell Cycle / drug effects*
  • Cell Division / drug effects
  • Cisplatin / pharmacology*
  • Flow Cytometry
  • Humans
  • Leukemia, T-Cell / pathology*
  • Tumor Cells, Cultured / drug effects

Substances

  • Antineoplastic Agents
  • DWA 2114
  • Carboplatin
  • Cisplatin