Effect of doxorubicin, daunorubicin, and idarubicin on the growth rate of human leukemia cells (K562) studied with image analysis.
The effects of doxorubicin, daunorubicin, and idarubicin on the growth of K562 cells were investigated by monitoring the formation of individual colonies in semi-solid culture employing an automated image analysis system. Drug effects were evaluated using short-term exposure (2 h) at clinically achievable drug plasma concentrations. Following drug exposure, heterogeneity in growth patterns was observed which was categorized into three distinct types; (1) continuous growth at a decreased growth rate; (2) limited growth; (3) no growth. In addition to a concentration-dependent decrease of the growth fraction, a reduction of the growth rate of the continuously growing colonies was observed. At equitoxic drug concentrations, comparable changes in growth rate were observed for each of the three anthracyclines studied. It is demonstrated that the fraction of cells which escape drug-induced growth arrest with therapeutically achievable drug concentrations display a significant decrease in growth rate.
Department of Experimental Therapeutics, Grace Cancer Drug Center, Roswell Park Cancer Institute, Buffalo, NY 14263.
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Minderman
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Slocum
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Malmberg
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Haanen
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Rustum
D002455:Cell Division / Q000187:drug effects; D003630:Daunorubicin / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology*; D006131:Growth Inhibitors; D006801:Humans; D015255:Idarubicin / Q000494:pharmacology*; D007091:Image Processing, Computer-Assisted; D066298:In Vitro Techniques; D014407:Tumor Cells, Cultured
D006131:Growth Inhibitors; D004317:Doxorubicin; D015255:Idarubicin; D003630:Daunorubicin