Comparison of Cell-Cycle Phase Perturbations Induced by the DNA-minor-groove Alkylator Tallimustine and by Melphalan in the SW626 Cell Line

Int J Cancer. 1995 Jul 17;62(2):170-5. doi: 10.1002/ijc.2910620211.

Abstract

Tallimustine or N-deformyl-N-[4-N-N,N-bis(2-chloroethylamino)benzoyl], a distamycin-A derivative (FCE 24517), is a novel anti-cancer agent which alkylates N3 adenine in the minor groove of DNA. The cell-cycle phase perturbations induced by the drug were investigated and compared with those caused by melphalan (L-PAM) in SW626 human ovarian-cancer cells. By coupling bromodeoxyuridine (BUdR) immunoreaction with biparametric flow-cytometric (FCM) analysis, we investigated the cell-cycle phase perturbation induced by tallimustine or L-PAM, considering separately the cells which, during the 1-hr treatment, were in the S phase or in G1-G2/M phases of the cell cycle. L-PAM delayed the S-phase progression of cells exposed to the drug when they were in S phase, with a consequent accumulation of cells as soon as they reached the G2 phase. In contrast, the S-phase cells treated with tallimustine were not perturbed during the DNA-synthesis phase progression, and were blocked in G2 only after they had passed through the G1/S transition of a new cell cycle. In cells which were in G1 or G2/M phases during drug treatment, tallimustine and L-PAM caused similar accumulation in G2. The differences in the cell-cycle perturbation caused by tallimustine and L-PAM may well be related to the different DNA damage the 2 drugs produced. These findings emphasize the different properties of DNA-minor-groove alkylating agents and conventional ones.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylating Agents / pharmacology*
  • Bromodeoxyuridine
  • Cell Cycle / drug effects*
  • DNA / chemistry*
  • DNA / ultrastructure
  • DNA, Neoplasm / analysis
  • Distamycins / pharmacology*
  • Female
  • Flow Cytometry
  • Humans
  • In Vitro Techniques
  • Melphalan / pharmacology*
  • Nitrogen Mustard Compounds / pharmacology*
  • Nucleic Acid Conformation
  • Ovarian Neoplasms
  • Tumor Cells, Cultured

Substances

  • Alkylating Agents
  • DNA, Neoplasm
  • Distamycins
  • Nitrogen Mustard Compounds
  • tallimustine
  • DNA
  • Bromodeoxyuridine
  • Melphalan