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Trypanosoma cruzi proliferation and differentiation are blocked by topoisomerase II inhibitors.
Gonzales-Perdomo, M; de Castro, S L; Meirelles, M N; Goldenberg, S.
Afiliação
  • Gonzales-Perdomo M; Departamento de Bioquimica e Biologia Molecular, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
Antimicrob Agents Chemother ; 34(9): 1707-14, 1990 Sep.
Article em En | MEDLINE | ID: mdl-2178335
Bacterial topoisomerase II inhibitors (ofloxacin and its commercial derivative Tarivid, nalidixic acid, and novobiocin) were tested as blockers of Trypanosoma cruzi differentiation and proliferation. The transformation of either epimastigotes into metacyclic trypomastigotes or amastigotes into trypomastigotes was inhibited by the drugs in a dose-dependent manner. The inhibition of epimastigote differentiation was also dependent on the time of drug addition to the medium. Proliferation of T. cruzi was also blocked in a dose-dependent manner by the drugs, with the exception of novobiocin, which did not inhibit epimastigote replication and resulted in cell lysis when it was used at high concentrations. On the other hand, the transformation of amastigotes into epimastigotes in axenic culture was not inhibited; this process did not require either kinetoplast (mitochondrial) DNA replication or changes in the DNA network organization. Electron microscopy of cells treated with Tarivid (ofloxacin) showed damage to the kinetoplast, suggesting that this organelle might be the target of the drug. These results indicate that a bacterial-like topoisomerase II plays an important role in T. cruzi proliferation and differentiation.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Trypanosoma cruzi / Inibidores da Topoisomerase II Limite: Animals Idioma: En Revista: Antimicrob Agents Chemother Ano de publicação: 1990 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Trypanosoma cruzi / Inibidores da Topoisomerase II Limite: Animals Idioma: En Revista: Antimicrob Agents Chemother Ano de publicação: 1990 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos