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Heloísa Helena Rodrigues de Andrade

Publications and source records attributed to Heloísa Helena Rodrigues de Andrade.

8 recordsLinked to original sources
PubMed2007

Effect of vanillin on toxicant-induced lethality in the Drosophila melanogaster DNA repair test.

Vanillin (VA) modulates the genotoxicity of chemical and physical agents in a complex manner. Previous studies indicate that VA inhibits the mutagenicity but increases the mitotic homologous recombination caused by at least some genotoxic agents. In the present study, we have evaluated the effects of VA on the repair of lethal damage produced by three genotoxins, N-ethyl-N-nitrosourea (ENU), ethyl methanesulfonate (EMS), and mitomycin C (MMC), using the DNA repair test (DRT) in Drosophila melanogaster. VA, 0.25% and 0.5% (w/v), increased the toxicity of MMC and EMS in repair-deficient flies, as measured by a decrease in the proportion of male to female progeny in the DRT; sex ratios decreased from 18-48% for MMC and 21-97% for EMS. These effects may be caused by the inhibition of nonhomologous DNA end joining caused by VA. In contrast to the results with MMC and EMS, VA protected against the lethality of ENU in repair-defective flies, as measured by a 43-207% increase in the survival of male flies in the DRT. It was inferred that the protective effect was due to VA modulating stages prior to the induction of ENU lesions in DNA, including modulating the antioxidant properties of VA and/or to its interference with the metabolic activation and/or detoxification of specific genotoxins. The results from this study indicate that the characterization of VA as a promising agent for preventing damage to genes and chromosomes should be tempered by observations that VA can increase the toxicity of chemical agents.

Animals↗
PubMed2006

Vanillin as a modulator agent in SMART test: inhibition in the steps that precede N-methyl-N-nitrosourea-, N-ethyl-N-nitrosourea-, ethylmethanesulphonate- and bleomycin-genotoxicity.

Vanillin (VA), the world's major flavoring compound used in food industry and confectionery products - that has antimutagenic and anticarcinogenic activity against a variety of mutagenic/carcinogenic agents - was tested for the interval between the formation of premutational lesion and it is finalization as a DNA lesion. The overall findings using co-treatment protocols in SMART test suggest that VA can lead to a significant protection against the general genotoxicity of ethylmethanesulphonate (EMS), N-ethyl-N-nitrosourea (ENU), N-methyl-N-nitrosourea (MNU) and bleomycin sulphate (BLEO). Considering MNU, ENU and EMS the desmutagenic activity observed could result from VA-stimulation of detoxification, via induction of glutathione S-transferase. However, the protector effect related to BLEO could be attributed to its powerful scavenger ability, which has the potential to prevent oxidative damage induced by BLEO.

Alkylating Agents↗
PubMed2005

Genotoxic effects of eugenol, isoeugenol and safrole in the wing spot test of Drosophila melanogaster.

In the present study, the phenolic compounds eugenol, isoeugenol and safrole were investigated for genotoxicity in the wing spot test of Drosophila melanogaster. The Drosophila wing somatic mutation and recombination test (SMART) provides a rapid means to evaluate agents able to induce gene mutations and chromosome aberrations, as well as rearrangements related to mitotic recombination. We applied the SMART in its standard version with normal bioactivation and in its variant with increased cytochrome P450-dependent biotransformation capacity. Eugenol and safrole produced a positive recombinagenic response only in the improved assay, which was related to a high CYP450-dependent activation capacity. This suggests, as previously reported, the involvement of this family of enzymes in the activation of eugenol and safrole rather than in its detoxification. On the contrary, isoeugenol was clearly non-genotoxic at the same millimolar concentrations as used for eugenol in both the crosses. The responsiveness of SMART assays to recombinagenic compounds, as well as the reactive metabolites from eugenol and safrole were considered responsible for the genotoxicity observed.

Animals↗
PubMed2004

Activity of topoisomerase inhibitors daunorubicin, idarubicin, and aclarubicin in the Drosophila Somatic Mutation and Recombination Test.

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 approximately 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.

Aclarubicin↗
PubMed2004

Effect of vanillin on toxicant-induced mutation and mitotic recombination in proliferating somatic cells of Drosophila melanogaster.

Vanillin (VA; C8H8O3) is a flavoring agent that in previous studies has both increased and decreased the genotoxicity of chemical agents, depending on the nature of both the agent and the genetic event measured. The ability of VA to modulate the mutagenicity and recombinogenicity of three different monoalkylating agents, N-ethyl-N-nitrosourea (ENU), N-methyl-N-nitrosourea (MNU), and ethyl methanesulfonate (EMS), and the intercalating agent bleomycin (BLEO) was examined using the somatic mutation and recombination test (SMART) in Drosophila melanogaster. While neither the mutagenicity nor the recombinagenicity of ENU or MNU was modified by posttreatment with VA, EMS-induced genetic toxicity was enhanced by as much as 30%. This overall enhancement included a synergistic increase in mitotic recombination and a lesser decrease in mutation. Posttreatment with VA also produced an increase in the genotoxicity of BLEO, which was characterized by increases of 120% and 180% for 0.5% and 1% VA, respectively. This enhancement was restricted to an increase in recombinational events, since no alteration in BLEO-induced mutation was observed. The data suggest that the major VA-modulatory action on genotoxicity in D. melanogaster is related to its synergistic effects on somatic recombination, which has a greater consequence on overall genotoxicity than its antimutagenic effects. Since the SMART assay is specifically sensitive to mitotic crossing-over, our data suggest that VA promotes toxicant-induced homologous recombination, at least in the proliferative cells of Drosophila.

Alkylating Agents↗
PubMed2003

Doxorubicin and two of its analogues are preferential inducers of homologous recombination compared with mutational events in somatic cells of Drosophila melanogaster.

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.

Animals↗
PubMed2002

Comparative genotoxic effect of vincristine, vinblastine, and vinorelbine in somatic cells of Drosophila melanogaster.

In this study, the vinca alkaloids vincristine (VCR), vinblastine (VBL) and vinorelbine (VNR) were investigated for genotoxicity in the wing Somatic Mutation and Recombination Test (SMART) of Drosophila. Our in vivo experiments demonstrated that all drugs assessed induced genetic toxicity, causing increments in the incidence of mutational events, as well as in somatic recombination. Another point to be considered is the fact that VNR was able to induce, respectively, approximately 13.0 and 1.7 times more mutant clones per millimolar exposure unit as their analogues VCR and VBL. The replacement of a CH(3) attached to vindoline group in VBL by a CHO in VCR seems to be responsible for the approximately seven times higher potency of the former. In contrast, the structural modifications on VNR's catharantine group could be related to its higher genotoxic potency, as well as its similar mutagenic and recombinagenic action.

Animals↗