title: Doxorubicin and two of its analogues are preferential inducers of homologous recombination compared with mutational events in somatic cells of Drosophila melanogaster.
abstract: The genotoxic effects of the anthracycline doxorubicin (DOX) and two of its analogues, epirubicin (EPI) and pirarubicin (THP) were studied using the wing Somatic Mutation and Recombination Test (SMART) in Drosophila melanogaster. These compounds are classified as topoisomerase II (topo II) poisons, acting by stabilizing a topoisomerase II-cleaved DNA complex. Using the standard version of the SMART test it was possible to estimate the quantitative and qualitative genotoxic effects of these compounds, comparing the wing spot frequencies in marker- and balancer-heterozygous flies. The results obtained indicate that all three compounds induce a high frequency of spots related to homologous recombination (HR), which is the major event responsible for their genetic toxicity. Pirarubicin was the most genotoxic anthracycline, inducing approximately 21 times more genetic lesions than doxorubicin, probably due to the presence of a second sugar ring in the amino sugar moiety in its chemical structure. Although the only difference between epirubicin and doxorubicin is the steric position of the amino sugar 4'-OH in the molecule, epirubicin is approximately 1.6 times as genotoxic as doxorubicin.
authors.affiliation: Departamento de Genética, Universidade Federal do Rio Grande do Sul, CP 15053, 91501-970, Porto Alegre, RS, Brazil.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Lehmann
authors.forename: Aline
authors.initials: A
authors.lastname: Franco
authors.forename: Knulp
authors.initials: K
authors.lastname: de Souza Prudente Vilar
authors.forename: Maria
authors.initials: M
authors.lastname: Luķza Reguly
authors.forename: Heloísa Helena Rodrigues
authors.initials: HH
authors.lastname: de Andrade
mesh_terms: D000818:Animals; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000633:toxicity*; D004331:Drosophila melanogaster / Q000187:drug effects / Q000235:genetics; D015251:Epirubicin / Q000633:toxicity*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D011995:Recombination, Genetic / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D009153:Mutagens; D015251:Epirubicin; D004317:Doxorubicin; C027260:pirarubicin