title: The synergistic effects of vanillin on recombination predominate over its antimutagenic action in relation to MMC-induced lesions in somatic cells of Drosophila melanogaster.
abstract: The wing Somatic Mutation And Recombination Test (SMART) in Drosophila melanogaster was used to study the modulating action of vanillin (VA) in combination with the alkylating agents mitomycin C (MMC), methylmethanesulphonate (MMS) and the bifunctional nitrogen mustard (HN2). Two types of treatments with VA and each of the three genotoxins were performed: chronic co-treatments of three-day-old larvae of the standard cross as well as post-treatments after acute exposure with the genotoxins. This allowed the study of the action of VA not only in the steps that precede the induction of DNA lesions but also in the repair processes. The overall findings from the co-treatment series suggest that ingestion of VA with MMS or MMC can lead to significant protection against genotoxicity; but this is not the case with HN2. Antioxidant activity, suppression of metabolic activation or interaction with the active groups of these two alkylating agents could be mechanisms by means of which VA exerts its desmutagenic action. In contrast, when evaluated in the post-treatment procedure, VA causes two antagonistic effects on the genotoxicity of MMC: (i) synergism on recombination (172.8%) and (ii) protection against mutation (79.0%). Consequently, both activities together lead to a considerable increase in mitotic recombination. In spite of being separate events, recombination and gene mutation are correlated during mitosis since the fate of a DNA lesion depends on the repair pathway followed. Our results may suggest that VA is a modifying factor that blocks the mutagenic pathway and consequently directs the MMC-induced lesions into a recombinational repair. Furthermore, VA did not modify the genotoxicity when administered after treatments with HN2 or MMS. Therefore, the major finding of the present study, namely the co-recombinagenic activity of VA on MMC-induced lesions, seems to be related to the type of induced lesion and consequently to the repair processes involved in its correction.
authors.affiliation: Laboratório de Mutagênese, Departamento de Genética, Universidade Federal do Rio Grande do Sul, CP 15053,91501-970, Porto Alegre, Brazil.
authors.forename: J H
authors.initials: JH
authors.lastname: Santos
authors.forename: U
authors.initials: U
authors.lastname: Graf
authors.forename: M L
authors.initials: ML
authors.lastname: Reguly
authors.forename: H H
authors.initials: HH
authors.lastname: Rodrigues de Andrade
mesh_terms: D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D001547:Benzaldehydes / Q000494:pharmacology*; D004331:Drosophila melanogaster; D004357:Drug Synergism; D005260:Female; D016685:Mitomycin / Q000633:toxicity*; D011995:Recombination, Genetic
chemical_list: D016587:Antimutagenic Agents; D001547:Benzaldehydes; D016685:Mitomycin; C100058:vanillin