The methylating agent streptozotocin induces persistent telomere dysfunction in mammalian cells

Autores
Paviolo, Natalia Soledad; Santiñaque, Federico F.; Castrogiovanni, Daniel Cayetano; Folle, Gustavo A.; Bolzan, Alejandro Daniel
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
We analyzed chromosomal aberrations involving telomeres in the progeny of mammalian cells exposed to the methylating agent and antineoplastic/diabetogenic drug streptozotocin (STZ), to test whether it induces long-term telomere instability (by chromosome end loss and/or telomere dysfunction). Rat cells (ADIPO-P2 cell line, derived from Sprague-Dawley rat adipose cells) were treated with a single concentration of STZ (2mM). Chromosomal aberrations were analyzed 18h, 10 days, and 15 days after treatment, using PNA-FISH with a pan-telomeric probe [Cy3-(CCCTAA)3] to detect (TTAGGG)n repeats. Cytogenetic analysis revealed a higher frequency of chromosomal aberrations in STZ-exposed cultures vs. untreated cultures at each time point analyzed. The yield of induced aberrations was very similar at each time point. Induction of aberrations not involving telomere dysfunction was only observed 18h and 15 days after treatment, whereas induction of telomere dysfunction-related aberrations by STZ (mainly in the form of telomere FISH signal loss and duplications, most of them chromatid-type aberrations) was observed at each time point. Our results show that STZ induces persistent telomere instability in mammalian cells, cytogenetically manifested as telomere dysfunction-related chromosomal aberrations. Neither telomere length nor telomerase activity is related to the telomere dysfunction.
Fil: Paviolo, Natalia Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina
Fil: Santiñaque, Federico F.. Instituto de Investigaciones Biológicas "Clemente Estable"; Uruguay
Fil: Castrogiovanni, Daniel Cayetano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina
Fil: Folle, Gustavo A.. Instituto de Investigaciones Biológicas "Clemente Estable"; Uruguay
Fil: Bolzan, Alejandro Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina
Materia
Long-Term Clastogenic Effect
Mammalian Cells
Streptozotocin
Telomere Dysfunction
Telomere Instability
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:11336/53652
Acceder
id CONICETDig_165bda85565a497abd09f21488710db4
oai_identifier_str oai:ri.conicet.gov.ar:11336/53652
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The methylating agent streptozotocin induces persistent telomere dysfunction in mammalian cellsPaviolo, Natalia SoledadSantiñaque, Federico F.Castrogiovanni, Daniel CayetanoFolle, Gustavo A.Bolzan, Alejandro DanielLong-Term Clastogenic EffectMammalian CellsStreptozotocinTelomere DysfunctionTelomere Instabilityhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1We analyzed chromosomal aberrations involving telomeres in the progeny of mammalian cells exposed to the methylating agent and antineoplastic/diabetogenic drug streptozotocin (STZ), to test whether it induces long-term telomere instability (by chromosome end loss and/or telomere dysfunction). Rat cells (ADIPO-P2 cell line, derived from Sprague-Dawley rat adipose cells) were treated with a single concentration of STZ (2mM). Chromosomal aberrations were analyzed 18h, 10 days, and 15 days after treatment, using PNA-FISH with a pan-telomeric probe [Cy3-(CCCTAA)3] to detect (TTAGGG)n repeats. Cytogenetic analysis revealed a higher frequency of chromosomal aberrations in STZ-exposed cultures vs. untreated cultures at each time point analyzed. The yield of induced aberrations was very similar at each time point. Induction of aberrations not involving telomere dysfunction was only observed 18h and 15 days after treatment, whereas induction of telomere dysfunction-related aberrations by STZ (mainly in the form of telomere FISH signal loss and duplications, most of them chromatid-type aberrations) was observed at each time point. Our results show that STZ induces persistent telomere instability in mammalian cells, cytogenetically manifested as telomere dysfunction-related chromosomal aberrations. Neither telomere length nor telomerase activity is related to the telomere dysfunction.Fil: Paviolo, Natalia Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Santiñaque, Federico F.. Instituto de Investigaciones Biológicas "Clemente Estable"; UruguayFil: Castrogiovanni, Daniel Cayetano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Folle, Gustavo A.. Instituto de Investigaciones Biológicas "Clemente Estable"; UruguayFil: Bolzan, Alejandro Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaElsevier Science2015-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/53652Paviolo, Natalia Soledad; Santiñaque, Federico F.; Castrogiovanni, Daniel Cayetano; Folle, Gustavo A.; Bolzan, Alejandro Daniel; The methylating agent streptozotocin induces persistent telomere dysfunction in mammalian cells; Elsevier Science; Mutation Research. Genetic Toxicology And Environmental Mutagenesis; 794; 12-2015; 17-241383-5718CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.mrgentox.2015.09.007info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1383571815002417info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:04:54Zoai:ri.conicet.gov.ar:11336/53652instacron: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:34982025-10-22 11:04:54.847CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The methylating agent streptozotocin induces persistent telomere dysfunction in mammalian cells
title The methylating agent streptozotocin induces persistent telomere dysfunction in mammalian cells
spellingShingle The methylating agent streptozotocin induces persistent telomere dysfunction in mammalian cells
Paviolo, Natalia Soledad
Long-Term Clastogenic Effect
Mammalian Cells
Streptozotocin
Telomere Dysfunction
Telomere Instability
title_short The methylating agent streptozotocin induces persistent telomere dysfunction in mammalian cells
title_full The methylating agent streptozotocin induces persistent telomere dysfunction in mammalian cells
title_fullStr The methylating agent streptozotocin induces persistent telomere dysfunction in mammalian cells
title_full_unstemmed The methylating agent streptozotocin induces persistent telomere dysfunction in mammalian cells
title_sort The methylating agent streptozotocin induces persistent telomere dysfunction in mammalian cells
dc.creator.none.fl_str_mv Paviolo, Natalia Soledad
Santiñaque, Federico F.
Castrogiovanni, Daniel Cayetano
Folle, Gustavo A.
Bolzan, Alejandro Daniel
author Paviolo, Natalia Soledad
author_facet Paviolo, Natalia Soledad
Santiñaque, Federico F.
Castrogiovanni, Daniel Cayetano
Folle, Gustavo A.
Bolzan, Alejandro Daniel
author_role author
author2 Santiñaque, Federico F.
Castrogiovanni, Daniel Cayetano
Folle, Gustavo A.
Bolzan, Alejandro Daniel
author2_role author
author
author
author
dc.subject.none.fl_str_mv Long-Term Clastogenic Effect
Mammalian Cells
Streptozotocin
Telomere Dysfunction
Telomere Instability
topic Long-Term Clastogenic Effect
Mammalian Cells
Streptozotocin
Telomere Dysfunction
Telomere Instability
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv We analyzed chromosomal aberrations involving telomeres in the progeny of mammalian cells exposed to the methylating agent and antineoplastic/diabetogenic drug streptozotocin (STZ), to test whether it induces long-term telomere instability (by chromosome end loss and/or telomere dysfunction). Rat cells (ADIPO-P2 cell line, derived from Sprague-Dawley rat adipose cells) were treated with a single concentration of STZ (2mM). Chromosomal aberrations were analyzed 18h, 10 days, and 15 days after treatment, using PNA-FISH with a pan-telomeric probe [Cy3-(CCCTAA)3] to detect (TTAGGG)n repeats. Cytogenetic analysis revealed a higher frequency of chromosomal aberrations in STZ-exposed cultures vs. untreated cultures at each time point analyzed. The yield of induced aberrations was very similar at each time point. Induction of aberrations not involving telomere dysfunction was only observed 18h and 15 days after treatment, whereas induction of telomere dysfunction-related aberrations by STZ (mainly in the form of telomere FISH signal loss and duplications, most of them chromatid-type aberrations) was observed at each time point. Our results show that STZ induces persistent telomere instability in mammalian cells, cytogenetically manifested as telomere dysfunction-related chromosomal aberrations. Neither telomere length nor telomerase activity is related to the telomere dysfunction.
Fil: Paviolo, Natalia Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina
Fil: Santiñaque, Federico F.. Instituto de Investigaciones Biológicas "Clemente Estable"; Uruguay
Fil: Castrogiovanni, Daniel Cayetano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina
Fil: Folle, Gustavo A.. Instituto de Investigaciones Biológicas "Clemente Estable"; Uruguay
Fil: Bolzan, Alejandro Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina
description We analyzed chromosomal aberrations involving telomeres in the progeny of mammalian cells exposed to the methylating agent and antineoplastic/diabetogenic drug streptozotocin (STZ), to test whether it induces long-term telomere instability (by chromosome end loss and/or telomere dysfunction). Rat cells (ADIPO-P2 cell line, derived from Sprague-Dawley rat adipose cells) were treated with a single concentration of STZ (2mM). Chromosomal aberrations were analyzed 18h, 10 days, and 15 days after treatment, using PNA-FISH with a pan-telomeric probe [Cy3-(CCCTAA)3] to detect (TTAGGG)n repeats. Cytogenetic analysis revealed a higher frequency of chromosomal aberrations in STZ-exposed cultures vs. untreated cultures at each time point analyzed. The yield of induced aberrations was very similar at each time point. Induction of aberrations not involving telomere dysfunction was only observed 18h and 15 days after treatment, whereas induction of telomere dysfunction-related aberrations by STZ (mainly in the form of telomere FISH signal loss and duplications, most of them chromatid-type aberrations) was observed at each time point. Our results show that STZ induces persistent telomere instability in mammalian cells, cytogenetically manifested as telomere dysfunction-related chromosomal aberrations. Neither telomere length nor telomerase activity is related to the telomere dysfunction.
publishDate 2015
dc.date.none.fl_str_mv 2015-12
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/11336/53652
Paviolo, Natalia Soledad; Santiñaque, Federico F.; Castrogiovanni, Daniel Cayetano; Folle, Gustavo A.; Bolzan, Alejandro Daniel; The methylating agent streptozotocin induces persistent telomere dysfunction in mammalian cells; Elsevier Science; Mutation Research. Genetic Toxicology And Environmental Mutagenesis; 794; 12-2015; 17-24
1383-5718
CONICET Digital
CONICET
url http://hdl.handle.net/11336/53652
identifier_str_mv Paviolo, Natalia Soledad; Santiñaque, Federico F.; Castrogiovanni, Daniel Cayetano; Folle, Gustavo A.; Bolzan, Alejandro Daniel; The methylating agent streptozotocin induces persistent telomere dysfunction in mammalian cells; Elsevier Science; Mutation Research. Genetic Toxicology And Environmental Mutagenesis; 794; 12-2015; 17-24
1383-5718
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.mrgentox.2015.09.007
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1383571815002417
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
dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv Elsevier Science
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 12.982451

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