Interference of tannic acid on the genotoxicity of mitomycin C, methylmethanesulfonate, and nitrogen mustard in somatic cells of Drosophila melanogaster.

The modulating effects of tannic acid (TA) on somatic mutation and mitotic recombination induced by methylmethanesulfonate (MMS), nitrogen mustard (HN2), and mitomycin C (MMC) were evaluated in the standard (ST) cross of the wing spot test in Drosophila melanogaster using co- and posttreatment protocols. It was shown that TA alone did not modify the spontaneous frequencies of single and twin spots, which means that this polyphenol neither acts as a genotoxin nor exerts any antigenotoxic effect over spontaneous DNA lesions. However, the simultaneous administration of genotoxins with TA can lead to considerable alterations of the frequencies of induced wing spots in comparison to those with administration of the genotoxins alone. In fact, TA produced a significant increase in HN2-induced wing spots with enhancements between 90 and 160%. For MMS, the enhancement was 38% in the highest TA concentration tested. In contrast, a significant protective action of this polyphenol was observed in combined treatments with MMC (64 to 99% inhibition). Moreover, the data from TA posttreatments demonstrated that this agent is not effective in exerting protective or enhancing effects on the genotoxicity of MMS, HN2, or MMC. One feasible mechanism of TA action is its interaction with the enzyme systems catalyzing the metabolic detoxification of MMS and HN2, which may also be involved in the bioactivation of MMC.

The synergistic effects of vanillin on recombination predominate over its antimutagenic action in relation to MMC-induced lesions in somatic cells of Drosophila melanogaster.

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.