Homologous recombination induced by doxazosin mesylate and saw palmetto in the Drosophila wing-spot test.
Benign prostatic hyperplasia (BPH) is the most common tumor in men over 40 years of age. Acute urinary retention (AUR) is regarded as the most serious hazard of untreated BPH. α-Blockers, such as doxazosin mesylate, and 5-α reductase inhibitors, such as finasteride, are frequently used because they decrease both AUR and the need for BPH-related surgery. An extract of the fruit from American saw palmetto plant has also been used as an alternative treatment for BPH. The paucity of information available concerning the genotoxic action of these compounds led us to assess their activity as inducers of different types of DNA lesions using the somatic mutation and recombination test in Drosophila melanogaster. Finasteride did not induce gene mutation, chromosomal mutation or mitotic recombination, which means it was nongenotoxic in our experimental conditions. On the other hand, doxazosin mesylate and saw palmetto induced significant increases in spot frequencies in trans-heterozygous flies. In order to establish the actual role played by mitotic recombination and by mutation in the genotoxicity observed, the balancer-heterozygous flies were also analyzed, showing no increment in the total spot frequencies in relation to the negative control, for both drugs. Doxazosin mesylate and saw palmetto were classified as specific inducers of homologous recombination in Drosophila proliferative cells, an event linked to the loss of heterozygosity.
Laboratório da Toxicidade Genética, Programa de Pós-Graduação em Genética e Toxicologia Aplicada, Universidade Luterana do Brasil, Canoas, RS, Brazil.
Katiane Cella
KC
Gabriel
Rafael Rodrigues
RR
Dihl
Mauricio
M
Lehmann
Maria Luiza
ML
Reguly
Marc François
MF
Richter
Heloisa Helena Rodrigues de
HH
Andrade
D000818:Animals; D000959:Antihypertensive Agents / Q000633:toxicity*; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D017292:Doxazosin / Q000633:toxicity*; D004330:Drosophila / Q000187:drug effects* / Q000235:genetics; D005260:Female; D019656:Loss of Heterozygosity / Q000187:drug effects; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D010936:Plant Extracts / Q000633:toxicity*; D011995:Recombination, Genetic / Q000187:drug effects*; D028024:Serenoa; D014921:Wings, Animal / Q000187:drug effects / Q000254:growth & development
D000959:Antihypertensive Agents; D009153:Mutagens; D010936:Plant Extracts; D004247:DNA; C040972:saw palmetto extract; D017292:Doxazosin