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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| Formato: | Tesis doctoral publishedVersion |
| Lenguaje: | Español |
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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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| Sumario: | 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. |
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