Direct and indirect clastogenic activity of anthracenedione in Chinese hamster ovary cells

The purpose of this study was to characterize the clastogenic activity of 1,4-dihydroxy-5,8-bis [[(2-[(2-hydroxyethyl)amino] ethyl)amino]]-9, 10-anthracenedione (NSC 301739), an antitumor compound now under clinical investigation. Chromosome damage in Chinese hamster ovary cells in G2 phase was assayed directly by the technique of premature chromosome condensation, and this damage was compared with the aberration levels determined when the G2 cells attained metaphase. 1,4-Dihydroxy-5,8-bis [[(2-[(2-hydroxyethyl)amino]ethyl)amino]]-9, 10-anthracenedione was observed to slow the progression of cells to mitosis and induce chromatid gaps, breaks, and exchanges directly in interphase cells. The frequency of gaps, breaks, and complete exchanges observed at metaphase were similar to those observed in G2 prematurely condensed chromosomes; however, the frequency of incomplete exchanges was increased in mitotic preparations. The additional exchanges appeared to result from chromosome stickiness occurring during chromosome condensation for metaphase. The chromosome attachments were strong and resulted in persistent chromosome bridges during anaphase. These results suggest that 1,4-dihydroxy-5,8-bis[[(2-[(2-hydroxyethyl)amino]ethyl)amino]]-9, 10-anthracenedione induces chromosome damage through both direct and indirect mechanisms.