Activity of topoisomerase inhibitors daunorubicin, idarubicin, and aclarubicin in the Drosophila Somatic Mutation and Recombination Test.
Anthracyclines have been widely used as anticancer drugs against different types of human cancers. The present study evaluated the mutagenic and recombinagenic properties of two anthracycline topoisomerase II (topo II) poisons, daunorubicin (DNR) and idarubicin (IDA), as well as the related topo II catalytic inhibitor aclarubicin (ACLA), using the wing Somatic Mutation and Recombination Test (SMART) in Drosophila melanogaster. The three anthracyclines were positive in this bioassay, producing mainly mitotic homologous recombination. The results for spot-size distribution and recombinagenic activity indicate that recombinational DNA damage accounts for approximately 91, 86, and 62% of DNR, IDA, and ACLA genotoxicity, respectively. Besides being a catalytic inhibitor of topo II, ACLA is also a topoisomerase I (topo I) poison. This dual topo I and II inhibitory effect, associated with its DNA-intercalating activity, could contribute to the activity of ACLA in the SMART assay.
Lehmann
Mauricio
M
Laboratório de Mutagênese, Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Vilar
Knulp de Souza Prudente
Kde S
Franco
Aline
A
Reguly
Maria Luíza
ML
Rodrigues de Andrade
Heloísa Helena
HH
D015250:Aclarubicin / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D001681:Biological Assay; D004252:DNA Mutational Analysis; D003630:Daunorubicin / Q000737:chemistry / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004330:Drosophila; D015255:Idarubicin / Q000737:chemistry / Q000633:toxicity*; D016296:Mutagenesis / Q000187:drug effects*; D059003:Topoisomerase Inhibitors; D014921:Wings, Animal / Q000033:anatomy & histology
D059003:Topoisomerase Inhibitors; D015250:Aclarubicin; D015255:Idarubicin; D003630:Daunorubicin