Cytotoxic and genotoxic effects of megazol, an anti-Chagas' disease drug, assessed by different short-term tests

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dc.contributor.authorPoli, P.
dc.contributor.authorMello, M. A. de
dc.contributor.authorBuschini, A.
dc.contributor.authorMortara, R. A.
dc.contributor.authorAlbuquerque, C. N. de
dc.contributor.authorSilva, S. da
dc.contributor.authorRossi, C.
dc.contributor.authorZucchi, TMAD
dc.contributor.institutionUniv Parma
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T12:33:37Z
dc.date.available2016-01-24T12:33:37Z
dc.date.issued2002-12-01
dc.description.abstractCyto- and genotoxicity induced by drugs can limit the dose and duration of treatment, can adversely affect patient quality of life, and may be life-threatening. Two drugs are currently being used for treatment of the acute phase of Chagas' disease and both have serious undesirable effects. in this research, cyto- and genotoxic activity of the nitroimidazole-tiadiazole derivative CL 64855 2-amino-5-(1-methyl-5-nitro-2-imidazolyl)-1,3,4-thiadiazole (megazol), a promising alternative drug, was evaluated in vitro with different short-term tests: (a) induction of recombination events and mutation in the yeast Saccharomyces cerevisiae D7 strain, with and without induction of cytochrome P-450; DNA damage (single and double strand breaks, alkali-labile sites, etc.) by the Comet assay in different mammalian cells. S. cerevisiae did not show a significant increase of mutant and recombinant event frequency,,both with and without cytochrome P450. On the other hand, the cytochrome complex appeared to detoxify the drug with respect to cytotoxicity. Results in rat and mouse fresh leukocytes showed a dose-response relation of drug-induced DNA damage. Findings in treated VERO cells suggested a complex treatment time-DNA damage relationship and the possible induction of repair mechanisms. Furthermore, bleomycin effects were increased in rat cells by simultaneous administration of megazol. Megazol shows different biological activity in relation to cellular types and experimental conditions (with or without cytochrome P-450, short/long time of exposure, with or without other genotoxins), thus suggesting a modulation of effectiveness by different physiological/biochemical conditions of cells. the findings could be useful to evaluate new megazol-derived compounds and to assess the risks/benefits relationship for each drug. (C) 2002 Elsevier Science Inc. All rights reserved.en
dc.description.affiliationUniv Parma, Ist Genet, I-43100 Parma, Italy
dc.description.affiliationUniv São Paulo, Inst Ciencias Biomed, Dept Parasitol, BR-05508900 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, EPM, Dept Microbiol Immunol & Parasitol, BR-04023062 São Paulo, Brazil
dc.description.affiliationUniv São Paulo, Fac Ciencias Farmaceut, Dept Tecnol Bioquim Farmaceut, BR-05508900 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, EPM, Dept Microbiol Immunol & Parasitol, BR-04023062 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.format.extent1617-1627
dc.identifierhttp://dx.doi.org/10.1016/S0006-2952(02)01390-4
dc.identifier.citationBiochemical Pharmacology. Oxford: Pergamon-Elsevier B.V., v. 64, n. 11, p. 1617-1627, 2002.
dc.identifier.doi10.1016/S0006-2952(02)01390-4
dc.identifier.issn0006-2952
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/27058
dc.identifier.wosWOS:000180208200008
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofBiochemical Pharmacology
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.subjectcomet assayen
dc.subjectDNA damageen
dc.subjectmutagenicityen
dc.subjectyeasten
dc.subjectanti-trypanosomal drugen
dc.subjectsynergetic effectsen
dc.subjectnitroimidazoleen
dc.titleCytotoxic and genotoxic effects of megazol, an anti-Chagas' disease drug, assessed by different short-term testsen
dc.typeinfo:eu-repo/semantics/article
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