Effects of a new antitumor agent, epipodophyllotoxin, on growth and chromosomes in human hematopoietic cell lines.

Abstract

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.