Protective effect of an antithyroid compound against γ-radiationinduced damage in human colon cancer cells

Autores
Perona, Marina; Dagrosa, María Alejandra; Pagotto, Romina María del Luján; Casal, Mariana; Pignataro, Omar Pedro; Pisarev, Mario Alberto; Juvenal, Guillermo Juan
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
We have previously reported the radioprotective effect of propylthiouracil (PTU) on thyroid cells. The aim of the present study was to analyze whether tumor cells and normal cells demonstrate the same response to PTU. Human colon carcinoma cells were irradiated with γ-irradiation with or without PTU. We evaluated the clonogenic survival, intracellular reactive oxygen species levels, catalase, superoxide dismutase and glutathione peroxidase activities, and apoptosis by nuclear cell morphology and caspase-3 activity assays. Cyclic AMP (cAMP) levels were measured by radioimmunoassay. PTU treatment increased surviving cell fraction at 2 Gy (SF2) from 56.9 ± 3.6 in controls to 75.0 ± 3.5 (p<0.05) and diminished radiation- induced apoptosis. In addition, we observed that the level of antioxidant enzymes’ activity was increased in cells treated with PTU. Moreover, pretreatment with PTU increased intracellular levels of cAMP. Forskolin (p<0.01) and dibutyryl cAMP (p<0.05) mimicked the effect of PTU on SF2. Co-treatment with H89, an inhibitor of protein kinase A, abolished the radioprotective effect of PTU. PTU reduces the toxicity of ionizing radiation by increasing cAMP levels and also possibly through a reduction in apoptosis levels and in radiation-induced oxidative stress damage. We therefore conclude that PTU protects both normal and cancer cells during exposure to radiation in conditions mimicking the radiotherapy.
Fil: Perona, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; Argentina
Fil: Dagrosa, María Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; Argentina
Fil: Pagotto, Romina María del Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Casal, Mariana. Comisión Nacional de Energía Atómica; Argentina
Fil: Pignataro, Omar Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Pisarev, Mario Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Juvenal, Guillermo Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; Argentina
Materia
Colon Cancer
Ionizing Radiation
Propylthiouracil
Radioprotection
Thyroid
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/76553
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/76553
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Protective effect of an antithyroid compound against γ-radiationinduced damage in human colon cancer cellsPerona, MarinaDagrosa, María AlejandraPagotto, Romina María del LujánCasal, MarianaPignataro, Omar PedroPisarev, Mario AlbertoJuvenal, Guillermo JuanColon CancerIonizing RadiationPropylthiouracilRadioprotectionThyroidhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1We have previously reported the radioprotective effect of propylthiouracil (PTU) on thyroid cells. The aim of the present study was to analyze whether tumor cells and normal cells demonstrate the same response to PTU. Human colon carcinoma cells were irradiated with γ-irradiation with or without PTU. We evaluated the clonogenic survival, intracellular reactive oxygen species levels, catalase, superoxide dismutase and glutathione peroxidase activities, and apoptosis by nuclear cell morphology and caspase-3 activity assays. Cyclic AMP (cAMP) levels were measured by radioimmunoassay. PTU treatment increased surviving cell fraction at 2 Gy (SF2) from 56.9 ± 3.6 in controls to 75.0 ± 3.5 (p<0.05) and diminished radiation- induced apoptosis. In addition, we observed that the level of antioxidant enzymes’ activity was increased in cells treated with PTU. Moreover, pretreatment with PTU increased intracellular levels of cAMP. Forskolin (p<0.01) and dibutyryl cAMP (p<0.05) mimicked the effect of PTU on SF2. Co-treatment with H89, an inhibitor of protein kinase A, abolished the radioprotective effect of PTU. PTU reduces the toxicity of ionizing radiation by increasing cAMP levels and also possibly through a reduction in apoptosis levels and in radiation-induced oxidative stress damage. We therefore conclude that PTU protects both normal and cancer cells during exposure to radiation in conditions mimicking the radiotherapy.Fil: Perona, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Dagrosa, María Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Pagotto, Romina María del Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Casal, Mariana. Comisión Nacional de Energía Atómica; ArgentinaFil: Pignataro, Omar Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Pisarev, Mario Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaFil: Juvenal, Guillermo Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaSpringer2014-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/76553Perona, Marina; Dagrosa, María Alejandra; Pagotto, Romina María del Luján; Casal, Mariana; Pignataro, Omar Pedro; et al.; Protective effect of an antithyroid compound against γ-radiationinduced damage in human colon cancer cells; Springer; Radiation and Environmental Biophysics; 53; 3; 4-2014; 611-6190301-634XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1007/s00411-014-0542-9info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007/s00411-014-0542-9info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:33:38Zoai:ri.conicet.gov.ar:11336/76553instacron: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 09:33:38.753CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Protective effect of an antithyroid compound against γ-radiationinduced damage in human colon cancer cells
title Protective effect of an antithyroid compound against γ-radiationinduced damage in human colon cancer cells
spellingShingle Protective effect of an antithyroid compound against γ-radiationinduced damage in human colon cancer cells
Perona, Marina
Colon Cancer
Ionizing Radiation
Propylthiouracil
Radioprotection
Thyroid
title_short Protective effect of an antithyroid compound against γ-radiationinduced damage in human colon cancer cells
title_full Protective effect of an antithyroid compound against γ-radiationinduced damage in human colon cancer cells
title_fullStr Protective effect of an antithyroid compound against γ-radiationinduced damage in human colon cancer cells
title_full_unstemmed Protective effect of an antithyroid compound against γ-radiationinduced damage in human colon cancer cells
title_sort Protective effect of an antithyroid compound against γ-radiationinduced damage in human colon cancer cells
dc.creator.none.fl_str_mv Perona, Marina
Dagrosa, María Alejandra
Pagotto, Romina María del Luján
Casal, Mariana
Pignataro, Omar Pedro
Pisarev, Mario Alberto
Juvenal, Guillermo Juan
author Perona, Marina
author_facet Perona, Marina
Dagrosa, María Alejandra
Pagotto, Romina María del Luján
Casal, Mariana
Pignataro, Omar Pedro
Pisarev, Mario Alberto
Juvenal, Guillermo Juan
author_role author
author2 Dagrosa, María Alejandra
Pagotto, Romina María del Luján
Casal, Mariana
Pignataro, Omar Pedro
Pisarev, Mario Alberto
Juvenal, Guillermo Juan
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Colon Cancer
Ionizing Radiation
Propylthiouracil
Radioprotection
Thyroid
topic Colon Cancer
Ionizing Radiation
Propylthiouracil
Radioprotection
Thyroid
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 have previously reported the radioprotective effect of propylthiouracil (PTU) on thyroid cells. The aim of the present study was to analyze whether tumor cells and normal cells demonstrate the same response to PTU. Human colon carcinoma cells were irradiated with γ-irradiation with or without PTU. We evaluated the clonogenic survival, intracellular reactive oxygen species levels, catalase, superoxide dismutase and glutathione peroxidase activities, and apoptosis by nuclear cell morphology and caspase-3 activity assays. Cyclic AMP (cAMP) levels were measured by radioimmunoassay. PTU treatment increased surviving cell fraction at 2 Gy (SF2) from 56.9 ± 3.6 in controls to 75.0 ± 3.5 (p<0.05) and diminished radiation- induced apoptosis. In addition, we observed that the level of antioxidant enzymes’ activity was increased in cells treated with PTU. Moreover, pretreatment with PTU increased intracellular levels of cAMP. Forskolin (p<0.01) and dibutyryl cAMP (p<0.05) mimicked the effect of PTU on SF2. Co-treatment with H89, an inhibitor of protein kinase A, abolished the radioprotective effect of PTU. PTU reduces the toxicity of ionizing radiation by increasing cAMP levels and also possibly through a reduction in apoptosis levels and in radiation-induced oxidative stress damage. We therefore conclude that PTU protects both normal and cancer cells during exposure to radiation in conditions mimicking the radiotherapy.
Fil: Perona, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; Argentina
Fil: Dagrosa, María Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; Argentina
Fil: Pagotto, Romina María del Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Casal, Mariana. Comisión Nacional de Energía Atómica; Argentina
Fil: Pignataro, Omar Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Pisarev, Mario Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Juvenal, Guillermo Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; Argentina
description We have previously reported the radioprotective effect of propylthiouracil (PTU) on thyroid cells. The aim of the present study was to analyze whether tumor cells and normal cells demonstrate the same response to PTU. Human colon carcinoma cells were irradiated with γ-irradiation with or without PTU. We evaluated the clonogenic survival, intracellular reactive oxygen species levels, catalase, superoxide dismutase and glutathione peroxidase activities, and apoptosis by nuclear cell morphology and caspase-3 activity assays. Cyclic AMP (cAMP) levels were measured by radioimmunoassay. PTU treatment increased surviving cell fraction at 2 Gy (SF2) from 56.9 ± 3.6 in controls to 75.0 ± 3.5 (p<0.05) and diminished radiation- induced apoptosis. In addition, we observed that the level of antioxidant enzymes’ activity was increased in cells treated with PTU. Moreover, pretreatment with PTU increased intracellular levels of cAMP. Forskolin (p<0.01) and dibutyryl cAMP (p<0.05) mimicked the effect of PTU on SF2. Co-treatment with H89, an inhibitor of protein kinase A, abolished the radioprotective effect of PTU. PTU reduces the toxicity of ionizing radiation by increasing cAMP levels and also possibly through a reduction in apoptosis levels and in radiation-induced oxidative stress damage. We therefore conclude that PTU protects both normal and cancer cells during exposure to radiation in conditions mimicking the radiotherapy.
publishDate 2014
dc.date.none.fl_str_mv 2014-04
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/11336/76553
Perona, Marina; Dagrosa, María Alejandra; Pagotto, Romina María del Luján; Casal, Mariana; Pignataro, Omar Pedro; et al.; Protective effect of an antithyroid compound against γ-radiationinduced damage in human colon cancer cells; Springer; Radiation and Environmental Biophysics; 53; 3; 4-2014; 611-619
0301-634X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/76553
identifier_str_mv Perona, Marina; Dagrosa, María Alejandra; Pagotto, Romina María del Luján; Casal, Mariana; Pignataro, Omar Pedro; et al.; Protective effect of an antithyroid compound against γ-radiationinduced damage in human colon cancer cells; Springer; Radiation and Environmental Biophysics; 53; 3; 4-2014; 611-619
0301-634X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1007/s00411-014-0542-9
info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007/s00411-014-0542-9
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
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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