TOPOISOMERASE INHIBITION BY LUCANTHONE, AN ADJUVANT IN RADIATION-THERAPY

Purpose: To determine whether lucanthone can inhibit human topoisomera ses in vitro. Methods and Materials: Lucanthone was incubated with hum an topoisomerases II and I together with their plasmid substrates, to determine if lucanthone interfered with the catalytic activities of to poisomerases and if it enhanced the formation of DNA strand breaks, as determined by agarose gel electrophoresis of the resultant plasmid fo rms. Results: Incubation of the enzymes with lucanthone inhibited the catalytic activity of topoisomerases II and I. With topoisomerase II, it increased the abundance of DNA double strand breaks (cleavable comp lexes). Conclusion: Lucanthone, like actinomycin D, inhibited topoisom erases II and I. It may act to enhance the yield of DNA double strand breaks in cells through a mechanism of topoisomerase LI inhibition. (C ) 1997 Elsevier Science Inc.