Cell cycle arrest and DNA damage after melphalan treatment of the human myeloma cell line RPMI 8226.
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.
Department of Oncology, Radiumhemmet, Karolinska Hospital, Stockholm, Sweden.
J O
JO
Fernberg
R
R
Lewensohn
S
S
Skog
D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects / Q000302:isolation & purification; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D008558:Melphalan / Q000494:pharmacology*; D010954:Plasmacytoma; D013997:Time Factors
D004273:DNA, Neoplasm; D008558:Melphalan