Mostrar el registro sencillo del ítem
dc.contributor.author
de Campos Nebel, Ildefonso Marcelo
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.contributor.author
Palmitelli, Micaela
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.contributor.author
Acevedo, S.
dc.contributor.author
Gonzalez Cid, Marcela Beatriz
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.date.available
2018-05-13T18:23:01Z
dc.date.issued
2016-12
dc.identifier.citation
de Campos Nebel, Ildefonso Marcelo; Palmitelli, Micaela; Acevedo, S.; Gonzalez Cid, Marcela Beatriz; Daño genético persistente inducido por venenos de topoisomerasa II en fibroblastos humanos normales: generación de inestabilidad cromosómica; Sociedad Argentina de Genética; Basic and Applied Genetics; XXVII; 2; 12-2016; 25-35
dc.identifier.issn
1666-0390
dc.identifier.uri
http://hdl.handle.net/11336/45028
dc.description.abstract
Topoisomerase II (Top2) poisons idarubicin (IDA) and etoposide (ETO) are anticancer drugs that target Top2 stabilizing DNA-enzymecomplexes and generating double-strand breaks (DSB). These DNA lesions are dangerous because they lead to genomic instability and promotetumorigenesis. These drugs are associated with the development of leukemias characterized by translocations of the MLL gene in treated patients.Our aim was to analyze the residual genetic damage induced by IDA and ETO in normal human fibroblasts at different times. Cells were treatedwith sublethal concentrations of IDA and ETO for 2 h and persistent DSB were evaluated in interphase nuclei and chromosomal aberrations (CA)in metaphase at 26 h post-treatment. In addition, micronuclei and MLL gene rearrangements were determined in interphase nuclei at 30 h posttreatment.Unrepaired persistent DSB induced by IDA and ETO turned into chromatid and chromosome breaks and improper repair in chromatidand chromosome exchanges. Simultaneously with increased CA, there was a marked reduction of the mitotic index, principally in cultures treatedwith IDA, due to the accumulation of cells in G2/M phase of cell cycle. This chromosomal damage progressed to the following interphase causingan increase in the micronucleated cells and in the rearrangements of MLL gene. The persistent DNA damage produced by IDA and ETO in normalhuman cells plays an important role in the possible induction of Top2 poisons-mediated secondary malignancies.
dc.description.abstract
Topoisomerase II (Top2) poisons idarubicin (IDA) and etoposide (ETO) are anticancer drugs that target Top2 stabilizing DNA-enzyme complexes and generating double-strand breaks (DSB). These DNA lesions are dangerous because they lead to genomic instability and promote tumorigenesis. These drugs are associated with the development of leukemias characterized by translocations of the MLL gene in treated patients. Our aim was to analyze the residual genetic damage induced by IDA and ETO in normal human fibroblasts at different times. Cells were treated with sublethal concentrations of IDA and ETO for 2 h and persistent DSB were evaluated in interphase nuclei and chromosomal aberrations (CA) in metaphase at 26 h post-treatment. In addition, micronuclei and MLL gene rearrangements were determined in interphase nuclei at 30 h posttreatment. Unrepaired persistent DSB induced by IDA and ETO turned into chromatid and chromosome breaks and improper repair in chromatid and chromosome exchanges. Simultaneously with increased CA, there was a marked reduction of the mitotic index, principally in cultures treated with IDA, due to the accumulation of cells in G2/M phase of cell cycle. This chromosomal damage progressed to the following interphase causing an increase in the micronucleated cells and in the rearrangements of MLL gene. The persistent DNA damage produced by IDA and ETO in normal human cells plays an important role in the possible induction of Top2 poisons-mediated secondary malignancies.
dc.format
application/pdf
dc.language.iso
spa
dc.publisher
Sociedad Argentina de Genética
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Idarubicina
dc.subject
Etoposido
dc.subject
Daño al Adn
dc.subject
Gen Mll
dc.subject
Idarubicin
dc.subject
Ectoposide
dc.subject
Dna Damage
dc.subject
Mll Gene
dc.subject.classification
Otras Ciencias Biológicas
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.subject.classification
Ciencias Biológicas
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.title
Daño genético persistente inducido por venenos de topoisomerasa II en fibroblastos humanos normales: generación de inestabilidad cromosómica
dc.title
Persistent genetic damage induced by topoisomerase II poisons in normal human fibroblasts: generation of chromoso me instability
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-04-16T14:29:37Z
dc.journal.volume
XXVII
dc.journal.number
2
dc.journal.pagination
25-35
dc.journal.pais
Argentina
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.journal.ciudad
Buenos Aires
dc.description.fil
Fil: de Campos Nebel, Ildefonso Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
dc.description.fil
Fil: Palmitelli, Micaela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
dc.description.fil
Fil: Acevedo, S.. Instituto de Investigaciones Hematológicas; Argentina
dc.description.fil
Fil: Gonzalez Cid, Marcela Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
dc.journal.title
Basic and Applied Genetics
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.scielo.org.ar/scielo.php?script=sci_arttext&pid=S1852-62332016000300003
Archivos asociados