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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 Cells¹

Memorial Sloan-Kettering Cancer Center, New York, New York 10021

9,10-Anthracenedione, 1,4-bis[[2-[(2-hydroxyethyl)amino]-ethyl]amino]-diacetate (NSC 287513), at concentrations ranging from 0.05 to 10.0 µg/ml, altered the cell cycle kinetics of Chinese hamster, Friend leukemia, and SK-L7 cells cultivated in vitro; the drug had little effect on cycle progression of normal phytohemagglutinin-stimulated lymphocytes. The major effect, following a 2- to 18-hr 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- and 18-hr 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 hr 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 to 0.2 µg/ml for 2 to 18 hr 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-hr treatment at 0.7 µg/ml. Stationary-phase-treated Chinese hamster cells were much more resistant to the drug action; 50% survival was observed following a 2-hr treatment at 10 µg/ml. The data suggest that, although the drug-induced cycle block is specific to the G₂ phase, the drug-induced kill is not cycle phase specific.

¹ Supported by Grant CA23296-01 from the National Cancer Institute.

² To whom requests for reprints should be addressed, at Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, N. Y. 10021.

Received 1/26/79. Accepted 4/ 4/79.