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Effects of a New Antitumor Agent, Epipodophyllotoxin, on Growth and Chromosomes in Human Hematopoietic Cell Lines¹

Springville Laboratories, Roswell Park Memorial Institute, Springville, New York 14141 [C. C. H., Y. H.], and Department of Pediatrics, Roswell Park Memorial Institute, Buffalo, New York 14203 [J. J. W.]

Treatment of four human hematopoietic cell lines, two derived from Burkitt lymphomas and two from the blood of normal persons, with the new antitumor agent epipodophyllotoxin (VP-16) for various durations at concentrations from 10^-7 to 10^-4 M caused severe inhibition of cell growth and a high incidence of cells with chromosome aberrations. The generation times of the lines, estimated by pulse labeling with thymidine-³H, ranged from 19 to 25 hr. Most of the aberrations observed in culture continuously treated with VP-16 were of the chromatid type. On the basis of generation times, types of aberrations, and data obtained in a culture pulsed with thymidine-³H and continuously treated with VP-16, it seems that aberrations were induced in the G₂ and S phases of the cell cycle. Cultures were also pulse treated with VP-16 for 1 hr at either 10^-4 or 10^-5 M. Growth inhibition and chromosome aberrations were again observed. Di- or multicentric chromosomes were common in the samples harvested 1 or 2 days after the pulse.

¹ This study was supported in part by NASA Contract NAS2-6679 and by NIH Research Grant CA-14011.

Received 7/19/73. Accepted 8/24/73.