Cell cycle arrest and DNA damage after melphalan treatment of the human myeloma cell line RPMI 8226

Eur J Haematol. 1991 Sep;47(3):161-7. doi: 10.1111/j.1600-0609.1991.tb01549.x.

Abstract

Exposure of a myeloma cell line (RPMI 8226) to a 30-minute pulse of melphalan (1-phenylalanine-mustard) resulted in a cell cycle progression delay characteristic for DNA cross-linking agents. Reduction of outflow of cells from late S- and G2-phases was more pronounced as compared to that from G1-phase. The consequence is a progressive accumulation of cells in late S- and G2-phases. At restoration of outflow of cells from late S- and G2-phases, complete removal of DNA interstrand cross-links, as measured by DNA alkaline elution, was noted. At this time less than 50% of maximum DNA-protein cross-links were removed. Further we found no correlation between restored outflow of cells from the G2-phase and removal of DNA-protein cross-links during the follow-up time of 72 h. No DNA double strand breaks as measured by DNA neutral elution were formed during the observation period. The data suggest that removal of DNA interstrand cross-links seems prerequisite for the outflow of cells from G2 after melphalan treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle / drug effects*
  • Cell Division / drug effects
  • Cell Line
  • DNA Damage*
  • DNA, Neoplasm / drug effects
  • DNA, Neoplasm / isolation & purification
  • Dose-Response Relationship, Drug
  • Humans
  • Kinetics
  • Melphalan / pharmacology*
  • Plasmacytoma
  • Time Factors

Substances

  • DNA, Neoplasm
  • Melphalan