THE PRODUCTION OF CHROMOSOMAL ALTERATIONS BY BETA-LAPACHONE, AN ACTIVATOR OF TOPOISOMERASE-I

The frequencies of chromosomal aberrations and sister-chromatid exchan ges (SCE) after exposure to beta-lapachone, an activator of mammalian topoisomerase I, were studied in Chinese hamster cells. A dose-depende nt increase in the frequencies of SCE was observed in continuous treat ments 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 therefo re propose that activation of topoisomerase I by beta-lapachone result s in the production of chromosomal alterations. The cell cycle depende nce of beta-lapachone clastogenic effects strongly suggests a mechanis m for the formation of chromosomal aberrations after this drug closely resembling the one observed for the topoisomerase I inhibitor, campto thecin.