Effect of doxorubicin exposure on cell-cycle kinetics of human leukemia cells studied by bivariate flow cytometric measurement of 5-iodo-2-deoxyuridine incorporation and DNA content.
Cell kinetics of two human leukemic cell lines, Molt-4 and K562, following a 2-h exposure to doxorubicin, were studied. DNA flow cytometry provided static information that for both cell lines a dose-dependent accumulation occurred at the G2 + M compartment that disappeared in time. Kinetic information was provided by time-monitoring cells labeled with 5-iodo-2-deoxyuridine (IdUrd) by two-parameter flow cytometry, analyzing the IdUrd label and the DNA content. The cell-cycle time (Tc) of exponentially growing Molt-4 cells was determined to be 20 h. Twenty-four hours after a 2-h exposure to 0.25 micrograms/ml doxorubicin, the Tc had increased to 23 h; following exposure to 1.0 micrograms/ml, it increased to 33 h. Cell kinetics of K562 cells following doxorubicin exposure were monitored in time up to 4 days. The average Tc of exponentially growing K562 cells was determined to be 24.7 h. Twenty-four hours following 2-h exposure to 0.25 or 0.5 micrograms/ml doxorubicin, the Tc were determined to be 28 and 32 h, respectively. After an additional 2 days, the Tc were both determined to be 24 h. The dose-dependent, reversible cell-cycle delay that persisted at least 48 h should be taken into account as an additional mode for decrease of a (tumor) cell population doubling time after exposure to doxorubicin.
Department of Hematology, University Hospital Nijmegen, The Netherlands.
H
H
Minderman
P P
PP
Brons
P C
PC
Linssen
A H
AH
Pennings
J M
JM
Wessels
J B
JB
Boezeman
C
C
Haanen
D002453:Cell Cycle / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000032:analysis*; D004317:Doxorubicin / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D007065:Idoxuridine / Q000378:metabolism*; D007700:Kinetics; D007938:Leukemia / Q000473:pathology*; D014407:Tumor Cells, Cultured
D004317:Doxorubicin; D004247:DNA; D007065:Idoxuridine