The production of chromosomal alterations by beta-lapachone, an activator of topoisomerase I.

ABSTRACT

The frequencies of chromosomal aberrations and sister-chromatid exchanges (SCE) after exposure to beta-lapachone, an activator of mammalian topoisomerase I, were studied in Chinese hamster cells. A dose-dependent increase in the frequencies of SCE was observed in continuous treatments with beta-lapachone. Chromatid-type aberrations were obtained in cells exposed to beta-lapachone for one cell cycle but also in cells exposed during the G2 phase of the cell cycle, with a marked induction of exchange-type aberrations for both treatment schedules. We therefore propose that activation of topoisomerase I by beta-lapachone results in the production of chromosomal alterations. The cell cycle dependence of beta-lapachone clastogenic effects strongly suggests a mechanism for the formation of chromosomal aberrations after this drug closely resembling the one observed for the topoisomerase I inhibitor, camptothecin.