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

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dc.contributor.author Poli, P.
dc.contributor.author Mello, M. A. de
dc.contributor.author Buschini, A.
dc.contributor.author Mortara, R. A.
dc.contributor.author Albuquerque, C. N. de
dc.contributor.author Silva, S. da
dc.contributor.author Rossi, C.
dc.contributor.author Zucchi, TMAD
dc.date.accessioned 2016-01-24T12:33:37Z
dc.date.available 2016-01-24T12:33:37Z
dc.date.issued 2002-12-01
dc.identifier http://dx.doi.org/10.1016/S0006-2952(02)01390-4
dc.identifier.citation Biochemical Pharmacology. Oxford: Pergamon-Elsevier B.V., v. 64, n. 11, p. 1617-1627, 2002.
dc.identifier.issn 0006-2952
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/27058
dc.description.abstract Cyto- 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.format.extent 1617-1627
dc.language.iso eng
dc.publisher Elsevier B.V.
dc.relation.ispartof Biochemical Pharmacology
dc.rights Acesso restrito
dc.subject comet assay en
dc.subject DNA damage en
dc.subject mutagenicity en
dc.subject yeast en
dc.subject anti-trypanosomal drug en
dc.subject synergetic effects en
dc.subject nitroimidazole en
dc.title Cytotoxic and genotoxic effects of megazol, an anti-Chagas' disease drug, assessed by different short-term tests en
dc.type Artigo
dc.rights.license http://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.contributor.institution Univ Parma
dc.contributor.institution Universidade de São Paulo (USP)
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.description.affiliation Univ Parma, Ist Genet, I-43100 Parma, Italy
dc.description.affiliation Univ São Paulo, Inst Ciencias Biomed, Dept Parasitol, BR-05508900 São Paulo, Brazil
dc.description.affiliation Universidade Federal de São Paulo, EPM, Dept Microbiol Immunol & Parasitol, BR-04023062 São Paulo, Brazil
dc.description.affiliation Univ São Paulo, Fac Ciencias Farmaceut, Dept Tecnol Bioquim Farmaceut, BR-05508900 São Paulo, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, EPM, Dept Microbiol Immunol & Parasitol, BR-04023062 São Paulo, Brazil
dc.identifier.doi 10.1016/S0006-2952(02)01390-4
dc.description.source Web of Science
dc.identifier.wos WOS:000180208200008



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