Efectos del tratamiento prolongado con AZT sobre células tumorales : acortamiento telomérico, inducción de senescencia y apoptosis, y reducción de tumorigenicidad

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Normal cells in culture divide a certain amount of times and undergo a processtermed replicative senescence. Telomere loss is thought to control entry intosenescence. Activation of telomerase in tumors bypasses cellular senescence and isthus a requirement for tumor progression. In this work, we have...

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Detalles Bibliográficos
Autor principal: Tejera, Agueda Mercedes
Otros Autores: Gomez, Daniel E.
Formato: Tesis doctoral publishedVersion
Lenguaje:Español
Publicado: Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales 2002
Materias:
APOPTOSIS
AZT
CANCER DE MAMA
SENESCENCIA
TELOMERASA
BREAST CANCER
SENESCENCE
TELOMERASE
Acceso en línea:https://hdl.handle.net/20.500.12110/tesis_n3502_Tejera
https://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=aextesis&d=tesis_n3502_Tejera_oai
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Repositorio Digital de la Universidad de Buenos Aires (UBA) de Universidad de Buenos Aires
id I28-R145-tesis_n3502_Tejera_oai
record_format dspace
spelling I28-R145-tesis_n3502_Tejera_oai2024-09-02 Gomez, Daniel E. Tejera, Agueda Mercedes 2002 Normal cells in culture divide a certain amount of times and undergo a processtermed replicative senescence. Telomere loss is thought to control entry intosenescence. Activation of telomerase in tumors bypasses cellular senescence and isthus a requirement for tumor progression. In this work, we have investigated theeffects of chronic in vitro 3'-azido-2', 3'-dideoxythymidine (AZT)exposure on humanand murine carcinoma cells. We demonstrate the irreversible telomere shortening inhuman cervical cancer cells (HeLa) cultured for long-term with AZT, but withoutevidence of senescence. Furthermore, we demonstrate, for the first time, that AZT-treatedmurine mammary carcinoma cells (F3II) have a reduced tumorigenicity insyngeneic BALB/c mice. Tumor incidence was reduced and survival was prolonged inanimals inoculated with AZT-treated cells when comparing with control counterparts. The number and size of spontaneous metastases were also decreased in animalsreceiving AZT-treated F3II cells. In addition, we present morphological and biochemicalevidence of senescence, and induction of apoptosis in tumor cells exposed to AZT. These data indicate that chronic exposure of mammary carcinoma cells to AZT may besufficient to induce a senescent phenotype and to reduce tumorigenicity. Fil: Tejera, Agueda Mercedes. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. application/pdf https://hdl.handle.net/20.500.12110/tesis_n3502_Tejera spa Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar APOPTOSIS AZT CANCER DE MAMA SENESCENCIA TELOMERASA APOPTOSIS AZT BREAST CANCER SENESCENCE TELOMERASE Efectos del tratamiento prolongado con AZT sobre células tumorales : acortamiento telomérico, inducción de senescencia y apoptosis, y reducción de tumorigenicidad Effects of AZT prolonged treatment on tumor cells: telomere shortening, induction of senescence and apoptosis and reduction of tumorigenicity info:eu-repo/semantics/doctoralThesis info:ar-repo/semantics/tesis doctoral info:eu-repo/semantics/publishedVersion https://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=aextesis&d=tesis_n3502_Tejera_oai
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-145
collection Repositorio Digital de la Universidad de Buenos Aires (UBA)
language Español
orig_language_str_mv spa
topic APOPTOSIS
AZT
CANCER DE MAMA
SENESCENCIA
TELOMERASA
APOPTOSIS
AZT
BREAST CANCER
SENESCENCE
TELOMERASE
spellingShingle APOPTOSIS
AZT
CANCER DE MAMA
SENESCENCIA
TELOMERASA
APOPTOSIS
AZT
BREAST CANCER
SENESCENCE
TELOMERASE
Tejera, Agueda Mercedes
Efectos del tratamiento prolongado con AZT sobre células tumorales : acortamiento telomérico, inducción de senescencia y apoptosis, y reducción de tumorigenicidad
topic_facet APOPTOSIS
AZT
CANCER DE MAMA
SENESCENCIA
TELOMERASA
APOPTOSIS
AZT
BREAST CANCER
SENESCENCE
TELOMERASE
description Normal cells in culture divide a certain amount of times and undergo a processtermed replicative senescence. Telomere loss is thought to control entry intosenescence. Activation of telomerase in tumors bypasses cellular senescence and isthus a requirement for tumor progression. In this work, we have investigated theeffects of chronic in vitro 3'-azido-2', 3'-dideoxythymidine (AZT)exposure on humanand murine carcinoma cells. We demonstrate the irreversible telomere shortening inhuman cervical cancer cells (HeLa) cultured for long-term with AZT, but withoutevidence of senescence. Furthermore, we demonstrate, for the first time, that AZT-treatedmurine mammary carcinoma cells (F3II) have a reduced tumorigenicity insyngeneic BALB/c mice. Tumor incidence was reduced and survival was prolonged inanimals inoculated with AZT-treated cells when comparing with control counterparts. The number and size of spontaneous metastases were also decreased in animalsreceiving AZT-treated F3II cells. In addition, we present morphological and biochemicalevidence of senescence, and induction of apoptosis in tumor cells exposed to AZT. These data indicate that chronic exposure of mammary carcinoma cells to AZT may besufficient to induce a senescent phenotype and to reduce tumorigenicity.
author2 Gomez, Daniel E.
author_facet Gomez, Daniel E.
Tejera, Agueda Mercedes
format Tesis doctoral
Tesis doctoral
publishedVersion
author Tejera, Agueda Mercedes
author_sort Tejera, Agueda Mercedes
title Efectos del tratamiento prolongado con AZT sobre células tumorales : acortamiento telomérico, inducción de senescencia y apoptosis, y reducción de tumorigenicidad
title_short Efectos del tratamiento prolongado con AZT sobre células tumorales : acortamiento telomérico, inducción de senescencia y apoptosis, y reducción de tumorigenicidad
title_full Efectos del tratamiento prolongado con AZT sobre células tumorales : acortamiento telomérico, inducción de senescencia y apoptosis, y reducción de tumorigenicidad
title_fullStr Efectos del tratamiento prolongado con AZT sobre células tumorales : acortamiento telomérico, inducción de senescencia y apoptosis, y reducción de tumorigenicidad
title_full_unstemmed Efectos del tratamiento prolongado con AZT sobre células tumorales : acortamiento telomérico, inducción de senescencia y apoptosis, y reducción de tumorigenicidad
title_sort efectos del tratamiento prolongado con azt sobre células tumorales : acortamiento telomérico, inducción de senescencia y apoptosis, y reducción de tumorigenicidad
publisher Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales
publishDate 2002
url https://hdl.handle.net/20.500.12110/tesis_n3502_Tejera
https://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=aextesis&d=tesis_n3502_Tejera_oai
work_keys_str_mv AT tejeraaguedamercedes efectosdeltratamientoprolongadoconaztsobrecelulastumoralesacortamientotelomericoinducciondesenescenciayapoptosisyreducciondetumorigenicidad
AT tejeraaguedamercedes effectsofaztprolongedtreatmentontumorcellstelomereshorteninginductionofsenescenceandapoptosisandreductionoftumorigenicity
_version_ 1824355303174438912

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