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Activity of topoisomerase inhibitors daunorubicin, idarubicin, and aclarubicin in the Drosophila Somatic Mutation and Recombination Test
Author(s) -
Lehmann Mauricio,
Vilar Knulp de Souza Prudente,
Franco Aline,
Reguly Maria Luíza,
de Andrade Heloísa Helena Rodrigues
Publication year - 2004
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.20023
Subject(s) - daunorubicin , topoisomerase , idarubicin , aclarubicin , genotoxicity , biology , anthracycline , microbiology and biotechnology , mutation , pharmacology , chemistry , doxorubicin , dna , biochemistry , genetics , gene , leukemia , toxicity , cytarabine , chemotherapy , organic chemistry , cancer , breast cancer
Abstract 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 ∼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. Environ. Mol. Mutagen. 43:250–257, 2004. © 2004 Wiley‐Liss, Inc.