Avaliação do potencial mutagênico e recombinogênico de fármacos através do teste SMART em Drosophila melanogaster: revisão
Palavras-chave:
Fármacos. Genotoxicidade. Teste SMART
Resumo
Fármacos são substâncias essenciais para a sobrevivência humana, já que curam doenças, amenizam dores, mantém o equilíbrio em determinadas disfunções e permitem a realização de cirurgias. Porém, apresentam muitos efeitos colaterais, entre os quais os genotóxicos são um dos mais preocupantes, já que podem ser o princípio de um câncer futuro. Para avaliar esses eventos genotóxicos existem alguns estudos, in vivo e in vitro. Entre os estudos in vivo, o teste de detecção de mutação e recombinação somática (SMART) em asas de Drosophila melanogaster demostra muitas vantagens como a detecção de diferentes tipos de danos genéticos, presença de genes homólogos a humanos e a não utilização de mamíferos. Portanto, essa revisão busca exemplificar o teste SMART, assim como, mostrar alguns estudos que avaliaram fármacos utilizados por humanos no tratamento de determinadas patologias, através desse teste.Referências
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ANDRADE, H.H.R.; REGULY, M.L.; LEHMANN M. Wing Somatic Mutation and Recombination Test (SMART). In: Henderson DS (ed). Drosophila Cytogenetics Protocols. The Humana Press Inc, p. 389-412, 2004.
DE MORAES FILHO, A.V.; DE JESUS SILVA CARVALHO, C; VERÇOSA, C.J; ET AL. In vivo genotoxicity evaluation of efavirenz (EFV) and tenofovir disoproxil fumarate (TDF) alone and in their clinical combinations in Drosophila melanogaster. Mutation Research , p. 31-38, 2017.
FRANCHI, L.P.; PENTIADO, N.H.; SILVA RDO N.; GUIMARÃES, N.N.; ET AL. Mutagenic and recombinagenic effects of lamivudine and stavudine antiretrovirals in somatic cells of Drosophila melanogaster. Food and Chemical Toxicology, p. 578-82, 2009.
FREI, H.; WÜRGLER, F.E. Statistical methods to decide whether mutagenicity test data from Drosophila assays indicate a positive, negative, or inconclusive result. Mutation Research, n. 203(4), p. 297-308, 1988.
FRÖLICH, A.; WÜRGLER, F.E. New tester strains with improved bioactivation capacity for the Drosophila wing-spot test. Mutation Research, n. 216, p. 179-87, 1989.
Guimarães, N.N; de Castro Pereira, K.; de Andrade, H.H; et al. Comparative analysis of genetic toxicity of azt and ddI antiretrovirals in somatic cells of Drosophila melanogaster. Environmental and Molecular Mutagenesis, p.312-7, 2008.
GRAF, U.; FREI, H.; KÄGI, A.; ET AL. Thirty compounds tested in the Drosophila wing spot test. Mutation Research, n. 222, p. 359-73, 1989.
GRAF, U.; WÜRGLER, F.E.; KATZ, A.J.; ET AL. Somatic mutation and recombination test in Drosophila melanogaster. Environmental and Molecular Mutagenesis, n. 6, p. 153-188, 1984.
HÄLLSTROM, I.; BLANCK, A. Genetic regulation of the cytochrome p-450 system in Drosophila melanogaster. I. chromosomal determination of some cytochrome p-450 dependent reactions. Chemico-Biological Interactions, n. 56, p. 157-71, 1985.
HINZ, J.M. Role of homologous recombination in DNA interstrand crosslink repair. Environmental and Molecular Mutagenesis, n. 51, p. 582-603, 2010.
KASTENBAUM, M.A.; BOWMAN, K.O. Tables for determining the statistical significance of mutation frequencies. Mutation Research, n.9(5), p. 527-49, 1970.
KOH, K; EVANS, J.M.; HENDRICKS, J.C.; ET AL. A Drosophila model for age-associated changes in sleep: wake cycles. Proceedings of the National Academy of Sciences of the United States of America, n. 103, p. 13843-47, 2006.
LARINI, L. Fármacos e medicamentos. Artmed. Porto Alegre, 2008.
LEHMANN M.;VILAR KDE, S.; FRANCO, A.; ET AL. Activity of topoisomerase inhibitors daunorubicin, idarubicin, and aclarubicin in the Drosophila Somatic Mutation and Recombination Test. Environmental and Molecular Mutagenesis, p. 250-7, 2004.
LUIZ, G.H.R.; MEZZAROBA, L. Efeitos tóxicos de Medicamentos decorrentes de erros de medição. Infarma, n. 7/8 p. 18-27, 2008.
MARCOS, R.; CARMONA, E.R. The wing-spot and the comet tests as useful assays detecting genotoxicity in Drosophila. Methods in Molecular Biology, n.1044, p. 417-27, 2013.
MARSH, J.L.; THOMPSON, L.M. Drosophila in the study of neurodegenerative disease. Neuron, n. 52, p. 169-78, 2006.
OLIVEIRA, V.C.; CONSTANTE, S.A.R.; ORSOLIN, P.C.; NEPOMUCENO, J.C.; ET AL. Modulatory effects of metformin on mutagenicity and epithelial tumor incidence in doxorubicin-treated Drosophila melanogaster. Food and Chemical Toxicology, p. 283-291, 2017.
ORSOLIN, P.C; SILVA-OLIVEIRA, R.G; NEPOMUCENO, J.C. Assessment of the mutagenic, recombinagenic and carcinogenic potential of orlistat in somatic cells of Drosophila melanogaster. Food and Chemical Toxicology, p. 2598-604, 2012.
SATURNINO, R.S.; MACHADO, N.M.; LOPES, J.C.; NEPOMUCENO, J.C. Assessment of the mutagenic, recombinogenic, and carcinogenic potential of amphotericin B in somatic cells of Drosophila melanogaster. Drug and Chemical Toxicology, n.9, p.1-7, 2017.
TALENS, F.; JALVING, M.; GIETEMA, J.A; VAN VUGT, M.A. Therapeutic targeting and patient selection for cancers with homologous recombination defects. Expert Opinion on Drug Discovery, n. 12(6), p. 565-581, 2017.
TIBURI, M.; REGULY, M.L; SCHWARTSMANN, G; CUNHA, K.S; ET AL. Comparative genotoxic effect of vincristine, vinblastine, and vinorelbine in somatic cells of Drosophila melanogaster. Mutation Research, p. 141-9, 2012.
YÜKSEL, M.; SARIKAYA, R.; BOSTANCI, N. Genotoxic evaluation of antiepileptic drugs by Drosophila somatic mutation and recombination test. Food and Chemical Toxicology, n. 48(10), p. 2682-7, 2010.
WU, B.; DAVEY, G.E.; NAZAROV, A.A.; DYSON, P.J.; DAVEY, CA. Specific DNA structural attributes modulate platinum anticancer drug site selection and cross-link generation. Nucleic Acids Research, n. 39, p. 8200-12, 2011.
ZAFRED, R.R.T; SPANO, M.A; MARTINS, R; ET AL. Pro-oxidant Activity and Genotoxicity of the Astronium fraxinifolium Using Wing SMART and Allium cepa Test. Journal of Medicinal Plants Research, n.10 (4), p. 276-285, 2016.
ZIJLSTRA, J.A.; VOGEL, E.W.; BREIMER, D.D. Pharmacological and toxicological aspects of mutagenicity research in Drosophila melanogaster. In: Hodgson E, Bend J, Philpot RM (eds) Reviews in biochemical toxicology, vol 8. Amsterdam: Elsevier, p. 121–154, 1987.
ANDRADE, H.H.R.; REGULY, M.L.; LEHMANN M. Wing Somatic Mutation and Recombination Test (SMART). In: Henderson DS (ed). Drosophila Cytogenetics Protocols. The Humana Press Inc, p. 389-412, 2004.
DE MORAES FILHO, A.V.; DE JESUS SILVA CARVALHO, C; VERÇOSA, C.J; ET AL. In vivo genotoxicity evaluation of efavirenz (EFV) and tenofovir disoproxil fumarate (TDF) alone and in their clinical combinations in Drosophila melanogaster. Mutation Research , p. 31-38, 2017.
FRANCHI, L.P.; PENTIADO, N.H.; SILVA RDO N.; GUIMARÃES, N.N.; ET AL. Mutagenic and recombinagenic effects of lamivudine and stavudine antiretrovirals in somatic cells of Drosophila melanogaster. Food and Chemical Toxicology, p. 578-82, 2009.
FREI, H.; WÜRGLER, F.E. Statistical methods to decide whether mutagenicity test data from Drosophila assays indicate a positive, negative, or inconclusive result. Mutation Research, n. 203(4), p. 297-308, 1988.
FRÖLICH, A.; WÜRGLER, F.E. New tester strains with improved bioactivation capacity for the Drosophila wing-spot test. Mutation Research, n. 216, p. 179-87, 1989.
Guimarães, N.N; de Castro Pereira, K.; de Andrade, H.H; et al. Comparative analysis of genetic toxicity of azt and ddI antiretrovirals in somatic cells of Drosophila melanogaster. Environmental and Molecular Mutagenesis, p.312-7, 2008.
GRAF, U.; FREI, H.; KÄGI, A.; ET AL. Thirty compounds tested in the Drosophila wing spot test. Mutation Research, n. 222, p. 359-73, 1989.
GRAF, U.; WÜRGLER, F.E.; KATZ, A.J.; ET AL. Somatic mutation and recombination test in Drosophila melanogaster. Environmental and Molecular Mutagenesis, n. 6, p. 153-188, 1984.
HÄLLSTROM, I.; BLANCK, A. Genetic regulation of the cytochrome p-450 system in Drosophila melanogaster. I. chromosomal determination of some cytochrome p-450 dependent reactions. Chemico-Biological Interactions, n. 56, p. 157-71, 1985.
HINZ, J.M. Role of homologous recombination in DNA interstrand crosslink repair. Environmental and Molecular Mutagenesis, n. 51, p. 582-603, 2010.
KASTENBAUM, M.A.; BOWMAN, K.O. Tables for determining the statistical significance of mutation frequencies. Mutation Research, n.9(5), p. 527-49, 1970.
KOH, K; EVANS, J.M.; HENDRICKS, J.C.; ET AL. A Drosophila model for age-associated changes in sleep: wake cycles. Proceedings of the National Academy of Sciences of the United States of America, n. 103, p. 13843-47, 2006.
LARINI, L. Fármacos e medicamentos. Artmed. Porto Alegre, 2008.
LEHMANN M.;VILAR KDE, S.; FRANCO, A.; ET AL. Activity of topoisomerase inhibitors daunorubicin, idarubicin, and aclarubicin in the Drosophila Somatic Mutation and Recombination Test. Environmental and Molecular Mutagenesis, p. 250-7, 2004.
LUIZ, G.H.R.; MEZZAROBA, L. Efeitos tóxicos de Medicamentos decorrentes de erros de medição. Infarma, n. 7/8 p. 18-27, 2008.
MARCOS, R.; CARMONA, E.R. The wing-spot and the comet tests as useful assays detecting genotoxicity in Drosophila. Methods in Molecular Biology, n.1044, p. 417-27, 2013.
MARSH, J.L.; THOMPSON, L.M. Drosophila in the study of neurodegenerative disease. Neuron, n. 52, p. 169-78, 2006.
OLIVEIRA, V.C.; CONSTANTE, S.A.R.; ORSOLIN, P.C.; NEPOMUCENO, J.C.; ET AL. Modulatory effects of metformin on mutagenicity and epithelial tumor incidence in doxorubicin-treated Drosophila melanogaster. Food and Chemical Toxicology, p. 283-291, 2017.
ORSOLIN, P.C; SILVA-OLIVEIRA, R.G; NEPOMUCENO, J.C. Assessment of the mutagenic, recombinagenic and carcinogenic potential of orlistat in somatic cells of Drosophila melanogaster. Food and Chemical Toxicology, p. 2598-604, 2012.
SATURNINO, R.S.; MACHADO, N.M.; LOPES, J.C.; NEPOMUCENO, J.C. Assessment of the mutagenic, recombinogenic, and carcinogenic potential of amphotericin B in somatic cells of Drosophila melanogaster. Drug and Chemical Toxicology, n.9, p.1-7, 2017.
TALENS, F.; JALVING, M.; GIETEMA, J.A; VAN VUGT, M.A. Therapeutic targeting and patient selection for cancers with homologous recombination defects. Expert Opinion on Drug Discovery, n. 12(6), p. 565-581, 2017.
TIBURI, M.; REGULY, M.L; SCHWARTSMANN, G; CUNHA, K.S; ET AL. Comparative genotoxic effect of vincristine, vinblastine, and vinorelbine in somatic cells of Drosophila melanogaster. Mutation Research, p. 141-9, 2012.
YÜKSEL, M.; SARIKAYA, R.; BOSTANCI, N. Genotoxic evaluation of antiepileptic drugs by Drosophila somatic mutation and recombination test. Food and Chemical Toxicology, n. 48(10), p. 2682-7, 2010.
WU, B.; DAVEY, G.E.; NAZAROV, A.A.; DYSON, P.J.; DAVEY, CA. Specific DNA structural attributes modulate platinum anticancer drug site selection and cross-link generation. Nucleic Acids Research, n. 39, p. 8200-12, 2011.
ZAFRED, R.R.T; SPANO, M.A; MARTINS, R; ET AL. Pro-oxidant Activity and Genotoxicity of the Astronium fraxinifolium Using Wing SMART and Allium cepa Test. Journal of Medicinal Plants Research, n.10 (4), p. 276-285, 2016.
ZIJLSTRA, J.A.; VOGEL, E.W.; BREIMER, D.D. Pharmacological and toxicological aspects of mutagenicity research in Drosophila melanogaster. In: Hodgson E, Bend J, Philpot RM (eds) Reviews in biochemical toxicology, vol 8. Amsterdam: Elsevier, p. 121–154, 1987.
Publicado
2018-06-22
Como Citar
Allgayer, N. (2018). Avaliação do potencial mutagênico e recombinogênico de fármacos através do teste SMART em Drosophila melanogaster: revisão. Revista Intertox De Toxicologia, Risco Ambiental E Sociedade, 11(2). https://doi.org/10.22280/revintervol11ed2.340
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