Efectos del tratamiento prolongado con AZT sobre células tumorales : acortamiento telomérico, inducción de senescencia y apoptosis, y reducción de tumorigenicidad
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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Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales
2002
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Acceso en línea: | https://hdl.handle.net/20.500.12110/tesis_n3502_Tejera |
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tesis:tesis_n3502_Tejera2023-10-02T19:49:35Z 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 Tejera, Agueda Mercedes Gomez, Daniel E. Alonso, Daniel F. APOPTOSIS AZT CANCER DE MAMA SENESCENCIA TELOMERASA APOPTOSIS AZT BREAST CANCER SENESCENCE TELOMERASE 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. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales 2002 info:eu-repo/semantics/doctoralThesis info:ar-repo/semantics/tesis doctoral info:eu-repo/semantics/publishedVersion application/pdf spa info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar https://hdl.handle.net/20.500.12110/tesis_n3502_Tejera |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-134 |
collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (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 |
work_keys_str_mv |
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_version_ |
1782022858350788608 |