Daño genético persistente inducido por venenos de topoisomerasa II en fibroblastos humanos normales: generación de inestabilidad cromosómica

Autores
de Campos Nebel, Ildefonso Marcelo; Palmitelli, Micaela; Acevedo, S.; Gonzalez Cid, Marcela Beatriz
Año de publicación
2016
Idioma
español castellano
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
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.
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
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
Fil: Acevedo, S.. Instituto de Investigaciones Hematológicas; Argentina
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
Materia
IDARUBICINA
ETOPOSIDO
DAÑO AL ADN
GEN MLL
IDARUBICIN
ECTOPOSIDE
DNA DAMAGE
MLL GENE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/45028
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/45028
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Daño genético persistente inducido por venenos de topoisomerasa II en fibroblastos humanos normales: generación de inestabilidad cromosómicaPersistent genetic damage induced by topoisomerase II poisons in normal human fibroblasts: generation of chromoso me instabilityde Campos Nebel, Ildefonso MarceloPalmitelli, MicaelaAcevedo, S.Gonzalez Cid, Marcela BeatrizIDARUBICINAETOPOSIDODAÑO AL ADNGEN MLLIDARUBICINECTOPOSIDEDNA DAMAGEMLL GENEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Topoisomerase 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.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.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; ArgentinaFil: Palmitelli, Micaela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Acevedo, S.. Instituto de Investigaciones Hematológicas; ArgentinaFil: 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; ArgentinaSociedad Argentina de Genética2016-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/45028de 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; 25-351666-0390CONICET DigitalCONICETspainfo:eu-repo/semantics/altIdentifier/url/http://www.scielo.org.ar/scielo.php?script=sci_arttext&pid=S1852-62332016000300003info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:37:05Zoai:ri.conicet.gov.ar:11336/45028instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 15:37:05.479CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Daño genético persistente inducido por venenos de topoisomerasa II en fibroblastos humanos normales: generación de inestabilidad cromosómica
Persistent genetic damage induced by topoisomerase II poisons in normal human fibroblasts: generation of chromoso me instability
title Daño genético persistente inducido por venenos de topoisomerasa II en fibroblastos humanos normales: generación de inestabilidad cromosómica
spellingShingle Daño genético persistente inducido por venenos de topoisomerasa II en fibroblastos humanos normales: generación de inestabilidad cromosómica
de Campos Nebel, Ildefonso Marcelo
IDARUBICINA
ETOPOSIDO
DAÑO AL ADN
GEN MLL
IDARUBICIN
ECTOPOSIDE
DNA DAMAGE
MLL GENE
title_short Daño genético persistente inducido por venenos de topoisomerasa II en fibroblastos humanos normales: generación de inestabilidad cromosómica
title_full Daño genético persistente inducido por venenos de topoisomerasa II en fibroblastos humanos normales: generación de inestabilidad cromosómica
title_fullStr Daño genético persistente inducido por venenos de topoisomerasa II en fibroblastos humanos normales: generación de inestabilidad cromosómica
title_full_unstemmed Daño genético persistente inducido por venenos de topoisomerasa II en fibroblastos humanos normales: generación de inestabilidad cromosómica
title_sort Daño genético persistente inducido por venenos de topoisomerasa II en fibroblastos humanos normales: generación de inestabilidad cromosómica
dc.creator.none.fl_str_mv de Campos Nebel, Ildefonso Marcelo
Palmitelli, Micaela
Acevedo, S.
Gonzalez Cid, Marcela Beatriz
author de Campos Nebel, Ildefonso Marcelo
author_facet de Campos Nebel, Ildefonso Marcelo
Palmitelli, Micaela
Acevedo, S.
Gonzalez Cid, Marcela Beatriz
author_role author
author2 Palmitelli, Micaela
Acevedo, S.
Gonzalez Cid, Marcela Beatriz
author2_role author
author
author
dc.subject.none.fl_str_mv IDARUBICINA
ETOPOSIDO
DAÑO AL ADN
GEN MLL
IDARUBICIN
ECTOPOSIDE
DNA DAMAGE
MLL GENE
topic IDARUBICINA
ETOPOSIDO
DAÑO AL ADN
GEN MLL
IDARUBICIN
ECTOPOSIDE
DNA DAMAGE
MLL GENE
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv 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.
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.
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
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
Fil: Acevedo, S.. Instituto de Investigaciones Hematológicas; Argentina
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
description 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.
publishDate 2016
dc.date.none.fl_str_mv 2016-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/45028
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
1666-0390
CONICET Digital
CONICET
url http://hdl.handle.net/11336/45028
identifier_str_mv 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
1666-0390
CONICET Digital
CONICET
dc.language.none.fl_str_mv spa
language spa
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.scielo.org.ar/scielo.php?script=sci_arttext&pid=S1852-62332016000300003
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Sociedad Argentina de Genética
publisher.none.fl_str_mv Sociedad Argentina de Genética
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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