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


Frei, Hansjörg; Würgler, Friedrich E (1996). Induction of somatic mutation and recombination by four inhibitors of eukaryotic topoisomerases assayed in the wing spot test of Drosophila melanogaster. Mutagenesis, 11(4):315-325.

Abstract

Four inhibitors of eukaryotic topoisomerases were investigated for genotoxic effects in the wing spot test of Drosophila melanogaster. As a somatic mutation and recombination test (SMART) this assay assesses mitotic recombination and mutational events of various kinds. We studied camptothecin as a topoisomerase I inhibitor, as well as ellipticine as an intercalating inhibitor and teniposide and etoposide as two non-intercalating inhibitors of topoisomerase II. Wing spots were induced in flies trans-heterozygous for the recessive wing cell markers multiple wing hairs (mwh) and flare (flr3) as well as in flies heterozygous for mwh and the multiply inverted TM3 balancer chromosome. All four compounds proved significantly genotoxic in this test The spot induction frequencies formally standardized to the millimolar unit of exposure dose decreased in the order camptothecin > teniposide > ellipticine ≳ etoposide in the mwh/flr3 inversion-free genotype. In the mwh/TM3 genotype, in which mitotic crossing over is suppressed because of the inversion-heterozygosity, the observed spot frequencies were considerably reduced, but to different extents. In this genotype, spot induction by ellipticine was not statistically significant, and it was determined that >99% of the spots are due to mitotic recombination in mwh/flr3 flies. For the other compounds, spot induction in the inversion-heterozygous genotype was significant. The relative contribution of recombination to total spot induction in the inversion-free genotype was 88% for camptothecin. It was significantly lower for the two epipodophyllotoxins teniposide (71%) and etoposide (59%). Only suggestions can be proffered at present as to how these proportions could be related to the primary damage produced by the respective compounds on the chromosomes

Abstract

Four inhibitors of eukaryotic topoisomerases were investigated for genotoxic effects in the wing spot test of Drosophila melanogaster. As a somatic mutation and recombination test (SMART) this assay assesses mitotic recombination and mutational events of various kinds. We studied camptothecin as a topoisomerase I inhibitor, as well as ellipticine as an intercalating inhibitor and teniposide and etoposide as two non-intercalating inhibitors of topoisomerase II. Wing spots were induced in flies trans-heterozygous for the recessive wing cell markers multiple wing hairs (mwh) and flare (flr3) as well as in flies heterozygous for mwh and the multiply inverted TM3 balancer chromosome. All four compounds proved significantly genotoxic in this test The spot induction frequencies formally standardized to the millimolar unit of exposure dose decreased in the order camptothecin > teniposide > ellipticine ≳ etoposide in the mwh/flr3 inversion-free genotype. In the mwh/TM3 genotype, in which mitotic crossing over is suppressed because of the inversion-heterozygosity, the observed spot frequencies were considerably reduced, but to different extents. In this genotype, spot induction by ellipticine was not statistically significant, and it was determined that >99% of the spots are due to mitotic recombination in mwh/flr3 flies. For the other compounds, spot induction in the inversion-heterozygous genotype was significant. The relative contribution of recombination to total spot induction in the inversion-free genotype was 88% for camptothecin. It was significantly lower for the two epipodophyllotoxins teniposide (71%) and etoposide (59%). Only suggestions can be proffered at present as to how these proportions could be related to the primary damage produced by the respective compounds on the chromosomes

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Item Type:Journal Article, refereed, original work
Communities & Collections:National licences > 142-005
Dewey Decimal Classification:Unspecified
Language:English
Date:1 January 1996
Deposited On:11 Oct 2018 14:01
Last Modified:24 Nov 2018 02:58
Publisher:Oxford University Press
ISSN:0267-8357
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/mutage/11.4.315
Related URLs:https://www.swissbib.ch/Search/Results?lookfor=nationallicenceoxford101093mutage114315 (Library Catalogue)

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