EFFECTS OF 9,10-ANTHRACENEDIONE, 1,4-BIS[[2-[(2-HYDROXYETHYL)AMINO]-ETHYL]AMINO]-DIACETATE ON CELL-SURVIVAL AND CELL-CYCLE PROGRESSION IN CULTURED MAMMALIAN-CELLS

9,10-Anthracenedione, 1,4-bis[[2-[(2-hydroxyethyl)amino]-ethyl]amino]-diacetate (NSC 287513), at concentrations ranging from 0.05-10.0 .mu.g/ml, altered the cell cycle kinetics of Chinese hamster [ovary, CHO], Friend leukemia [strain 745, mouse], and SK-L7 [human acute myelomonocytic leukemia] cells cultivated in vitro; the drug had little effect on cycle progression of normal phytohemagglutinin-stimulated lymphocytes. The major effect, following a 2-18 h exposure to drug, was a block of cell cycle progression at the G2-M phases as determined by flow cytometry. Although the mode of blocking action was concentration dependent, the results were similar for both a 2-18 h drug treatment. Blocked cells typically had an increased amount of cellular RNA and in some cases abnormally large nucleoli. The terminal point of action in Friend leukemia cells occurred about 3 h prior to mitosis, or within the last quarter of S phase. Unique to Friend leukemia cells was the observation that after drug treatment, at concentrations of 0.05-0.2 .mu.g/ml for 2-18 h followed by cell transfer to normal media, approximately 30% of the cells entered the cycle at a higher ploidy level. Survival curves on treated log phase Chinese hamster cells indicated that the cell kill response was straight line exponential; 50% survival (measured by colony formation) occurred following a 2 h treatment at 0.7 .mu.g/ml. Stationary-phase-treated Chinese hamster cells were much more resistant to the drug action; 50% survival was observed following a 2 h treatment at 10 .mu.g/ml. Although the drug-induced cycle block is specific to the G2 phase, the drug-induced kill is apparently not cycle phase specific.