Correlation between chromosome damage and apoptosis induced by fludarabine and idarubicin in normal human lymphocytes

Autores
Gonzalez Cid, Marcela Beatriz; Fundia, Ariela Freya; Cuello, María Teresa; Larripa, Irene Beatriz
Año de publicación
2002
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Fludarabine (FLU, a fluorinated purine analog) and idarubicin (IDA, a DNA-topoisomerase II poison) are frequently used in cancer chemotherapy. The effects of these drugs on cultured normal human lymphocytes were studied to establish the possible involvement of chromosome damage in the apoptotic program. Chromosome aberrations (CA) were evaluated in first division metaphases and the apoptotic process was measured by morphological and electrophoretical techniques. The percentage of abnormal cells was increased from the doses of FLU 1.0 μg/ml and IDA 0.005 μg/ml (P<0.0001) with an important decrease in the mitotic index (MI) for the highest doses assayed. A significant dose-dependent induction of abnormal cells was observed for both drugs. An increase of apoptotic cells was found at 5.0 and 10.0 μg/ml of FLU (P<0.001) while IDA activated apoptosis at 0.05 μg/ml (P<0.01) and markedly from 0.1 μg/ml (P<0.001). These increments were dose dependent. Apoptotic cell morphology was associated with DNA fragmentation at the highest doses. The increased induction of abnormal cells and the decreased MI were in correlation with the apoptotic index for FLU and IDA, suggesting the role of CA in drug-induced cell death.
Fil: Gonzalez Cid, Marcela Beatriz. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Fundia, Ariela Freya. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina
Fil: Cuello, María Teresa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina
Fil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina
Materia
Apoptosis
Chromosome Aberrations
Fludarabine
Idarubicin
Normal Human Lymphocytes
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/55008
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/55008
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Correlation between chromosome damage and apoptosis induced by fludarabine and idarubicin in normal human lymphocytesGonzalez Cid, Marcela BeatrizFundia, Ariela FreyaCuello, María TeresaLarripa, Irene BeatrizApoptosisChromosome AberrationsFludarabineIdarubicinNormal Human Lymphocyteshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Fludarabine (FLU, a fluorinated purine analog) and idarubicin (IDA, a DNA-topoisomerase II poison) are frequently used in cancer chemotherapy. The effects of these drugs on cultured normal human lymphocytes were studied to establish the possible involvement of chromosome damage in the apoptotic program. Chromosome aberrations (CA) were evaluated in first division metaphases and the apoptotic process was measured by morphological and electrophoretical techniques. The percentage of abnormal cells was increased from the doses of FLU 1.0 μg/ml and IDA 0.005 μg/ml (P<0.0001) with an important decrease in the mitotic index (MI) for the highest doses assayed. A significant dose-dependent induction of abnormal cells was observed for both drugs. An increase of apoptotic cells was found at 5.0 and 10.0 μg/ml of FLU (P<0.001) while IDA activated apoptosis at 0.05 μg/ml (P<0.01) and markedly from 0.1 μg/ml (P<0.001). These increments were dose dependent. Apoptotic cell morphology was associated with DNA fragmentation at the highest doses. The increased induction of abnormal cells and the decreased MI were in correlation with the apoptotic index for FLU and IDA, suggesting the role of CA in drug-induced cell death.Fil: Gonzalez Cid, Marcela Beatriz. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fundia, Ariela Freya. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; ArgentinaFil: Cuello, María Teresa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; ArgentinaFil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; ArgentinaElsevier Ireland2002-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/55008Gonzalez Cid, Marcela Beatriz; Fundia, Ariela Freya; Cuello, María Teresa; Larripa, Irene Beatriz; Correlation between chromosome damage and apoptosis induced by fludarabine and idarubicin in normal human lymphocytes; Elsevier Ireland; Toxicology; 171; 2-3; 2-2002; 215-2220300-483XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0300483X01005960info:eu-repo/semantics/altIdentifier/doi/10.1016/S0300-483X(01)00596-0info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:32:58Zoai:ri.conicet.gov.ar:11336/55008instacron: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:34982025-09-29 10:32:58.947CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Correlation between chromosome damage and apoptosis induced by fludarabine and idarubicin in normal human lymphocytes
title Correlation between chromosome damage and apoptosis induced by fludarabine and idarubicin in normal human lymphocytes
spellingShingle Correlation between chromosome damage and apoptosis induced by fludarabine and idarubicin in normal human lymphocytes
Gonzalez Cid, Marcela Beatriz
Apoptosis
Chromosome Aberrations
Fludarabine
Idarubicin
Normal Human Lymphocytes
title_short Correlation between chromosome damage and apoptosis induced by fludarabine and idarubicin in normal human lymphocytes
title_full Correlation between chromosome damage and apoptosis induced by fludarabine and idarubicin in normal human lymphocytes
title_fullStr Correlation between chromosome damage and apoptosis induced by fludarabine and idarubicin in normal human lymphocytes
title_full_unstemmed Correlation between chromosome damage and apoptosis induced by fludarabine and idarubicin in normal human lymphocytes
title_sort Correlation between chromosome damage and apoptosis induced by fludarabine and idarubicin in normal human lymphocytes
dc.creator.none.fl_str_mv Gonzalez Cid, Marcela Beatriz
Fundia, Ariela Freya
Cuello, María Teresa
Larripa, Irene Beatriz
author Gonzalez Cid, Marcela Beatriz
author_facet Gonzalez Cid, Marcela Beatriz
Fundia, Ariela Freya
Cuello, María Teresa
Larripa, Irene Beatriz
author_role author
author2 Fundia, Ariela Freya
Cuello, María Teresa
Larripa, Irene Beatriz
author2_role author
author
author
dc.subject.none.fl_str_mv Apoptosis
Chromosome Aberrations
Fludarabine
Idarubicin
Normal Human Lymphocytes
topic Apoptosis
Chromosome Aberrations
Fludarabine
Idarubicin
Normal Human Lymphocytes
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Fludarabine (FLU, a fluorinated purine analog) and idarubicin (IDA, a DNA-topoisomerase II poison) are frequently used in cancer chemotherapy. The effects of these drugs on cultured normal human lymphocytes were studied to establish the possible involvement of chromosome damage in the apoptotic program. Chromosome aberrations (CA) were evaluated in first division metaphases and the apoptotic process was measured by morphological and electrophoretical techniques. The percentage of abnormal cells was increased from the doses of FLU 1.0 μg/ml and IDA 0.005 μg/ml (P<0.0001) with an important decrease in the mitotic index (MI) for the highest doses assayed. A significant dose-dependent induction of abnormal cells was observed for both drugs. An increase of apoptotic cells was found at 5.0 and 10.0 μg/ml of FLU (P<0.001) while IDA activated apoptosis at 0.05 μg/ml (P<0.01) and markedly from 0.1 μg/ml (P<0.001). These increments were dose dependent. Apoptotic cell morphology was associated with DNA fragmentation at the highest doses. The increased induction of abnormal cells and the decreased MI were in correlation with the apoptotic index for FLU and IDA, suggesting the role of CA in drug-induced cell death.
Fil: Gonzalez Cid, Marcela Beatriz. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Fundia, Ariela Freya. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina
Fil: Cuello, María Teresa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina
Fil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina
description Fludarabine (FLU, a fluorinated purine analog) and idarubicin (IDA, a DNA-topoisomerase II poison) are frequently used in cancer chemotherapy. The effects of these drugs on cultured normal human lymphocytes were studied to establish the possible involvement of chromosome damage in the apoptotic program. Chromosome aberrations (CA) were evaluated in first division metaphases and the apoptotic process was measured by morphological and electrophoretical techniques. The percentage of abnormal cells was increased from the doses of FLU 1.0 μg/ml and IDA 0.005 μg/ml (P<0.0001) with an important decrease in the mitotic index (MI) for the highest doses assayed. A significant dose-dependent induction of abnormal cells was observed for both drugs. An increase of apoptotic cells was found at 5.0 and 10.0 μg/ml of FLU (P<0.001) while IDA activated apoptosis at 0.05 μg/ml (P<0.01) and markedly from 0.1 μg/ml (P<0.001). These increments were dose dependent. Apoptotic cell morphology was associated with DNA fragmentation at the highest doses. The increased induction of abnormal cells and the decreased MI were in correlation with the apoptotic index for FLU and IDA, suggesting the role of CA in drug-induced cell death.
publishDate 2002
dc.date.none.fl_str_mv 2002-02
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/11336/55008
Gonzalez Cid, Marcela Beatriz; Fundia, Ariela Freya; Cuello, María Teresa; Larripa, Irene Beatriz; Correlation between chromosome damage and apoptosis induced by fludarabine and idarubicin in normal human lymphocytes; Elsevier Ireland; Toxicology; 171; 2-3; 2-2002; 215-222
0300-483X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/55008
identifier_str_mv Gonzalez Cid, Marcela Beatriz; Fundia, Ariela Freya; Cuello, María Teresa; Larripa, Irene Beatriz; Correlation between chromosome damage and apoptosis induced by fludarabine and idarubicin in normal human lymphocytes; Elsevier Ireland; Toxicology; 171; 2-3; 2-2002; 215-222
0300-483X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0300483X01005960
info:eu-repo/semantics/altIdentifier/doi/10.1016/S0300-483X(01)00596-0
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Ireland
publisher.none.fl_str_mv Elsevier Ireland
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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score 13.070432

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