Induction of somatic mutation and recombination by four inhibitors of eukaryotic topoisomerases assayed in the wing spot test of Drosophila melanogaster

Four inhibitors of eukaryotic topoisomerases were investigatedfor genotoxic effects in the wing spot test of Drosophila melanogaster.As a somatic mutation and recombination test (SMART) this assayassesses mitotic recombination and mutational events of variouskinds. We studied camptothecin as a topoisomerase I inhibitor,as well as ellipticine as an intercalating inhibitor and teniposideand etoposide as two non-intercalating inhibitors of topoisomeraseII. Wing spots were induced in flies trans-heterozygous forthe recessive wing cell markers multiple wing hairs (mwh) andflare (flr³) as well as in flies heterozygous for mwh and themultiply inverted TM3 balancer chromosome. All four compoundsproved significantly genotoxic in this test The spot inductionfrequencies formally standardized to the millimolar unit ofexposure dose decreased in the order camptothecin > teniposide> ellipticine