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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.