Protection against radiation-induced damage of 6-propyl-2-thiouracil (PTU) in thyroid cells

Autores
Perona, Marina; Dagrosa, Maria Alejandra; Pagotto, Romina María del Luján; Casal, Mariana; Pignataro, Omar Pedro; Pisarev, Mario Alberto; Juvenal, Guillermo Juan
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Many epidemiologic studies have shown that the exposure to high external radiation doses increases thyroid neoplastic frequency, especially when given during childhood or adolescence. The use of radioprotective drugs may decrease the damage caused by radiation therapy and therefore could be useful to prevent the development of thyroid tumors. The aim of this study was to investigate the possible application of 6-propyl-2-thiouracil (PTU) as a radioprotector in the thyroid gland. Rat thyroid epithelial cells (FRTL-5) were exposed to different doses of g irradiation with or without the addition of PTU, methimazole (MMI), reduced glutathione (GSH) and perchlorate (KClO4). Radiation response was analyzed by clonogenic survival assay. Cyclic AMP (cAMP) levels were measured by radioimmunoassay (RIA). Apoptosis was quantified by nuclear cell morphology and caspase 3 activity assays. Intracellular reactive oxygen species (ROS) levels were measured using the fluorescent dye 20,70-dichlorofluorescein- diacetate. Catalase, superoxide dismutase and glutathione peroxidase activities were also determined. Pretreatment with PTU, MMI and GSH prior to irradiation significantly increased the surviving cell fraction (SF) at 2 Gy (P , 0.05), while no effect was observed with KClO4. An increase in extracellular levels of cAMP was found only in PTU treated cells in a dose and timedependent manner. Cells incubated with agents that stimulate cAMP (forskolin and dibutyril cAMP) mimicked the effect of PTU on SF. Moreover, pretreatment with the inhibitor of protein kinase A, H-89, abolished the radioprotective effect of PTU. PTU treatment diminished radiation-induced apoptosis and protected cells against radiation-induced ROS elevation and suppression of the antioxidant enzyme?s activity. PTU was found to radioprotect normal thyroid cells through cAMP elevation and reduction in both apoptosis and radiation-induced oxidative stress damage.
Fil: Perona, Marina. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (centro Atómico Constituyentes); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Dagrosa, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina
Fil: Pagotto, Romina María del Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Casal, Mariana. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncologí­a "Angel H. Roffo"; Argentina
Fil: Pignataro, Omar Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Pisarev, Mario Alberto. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Juvenal, Guillermo Juan. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (centro Atómico Constituyentes); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Radioprotector
Thyroid
Propylthiouracil
Cancer
Camp
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:11336/9010
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Protection against radiation-induced damage of 6-propyl-2-thiouracil (PTU) in thyroid cellsPerona, MarinaDagrosa, Maria AlejandraPagotto, Romina María del LujánCasal, MarianaPignataro, Omar PedroPisarev, Mario AlbertoJuvenal, Guillermo JuanRadioprotectorThyroidPropylthiouracilCancerCamphttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Many epidemiologic studies have shown that the exposure to high external radiation doses increases thyroid neoplastic frequency, especially when given during childhood or adolescence. The use of radioprotective drugs may decrease the damage caused by radiation therapy and therefore could be useful to prevent the development of thyroid tumors. The aim of this study was to investigate the possible application of 6-propyl-2-thiouracil (PTU) as a radioprotector in the thyroid gland. Rat thyroid epithelial cells (FRTL-5) were exposed to different doses of g irradiation with or without the addition of PTU, methimazole (MMI), reduced glutathione (GSH) and perchlorate (KClO4). Radiation response was analyzed by clonogenic survival assay. Cyclic AMP (cAMP) levels were measured by radioimmunoassay (RIA). Apoptosis was quantified by nuclear cell morphology and caspase 3 activity assays. Intracellular reactive oxygen species (ROS) levels were measured using the fluorescent dye 20,70-dichlorofluorescein- diacetate. Catalase, superoxide dismutase and glutathione peroxidase activities were also determined. Pretreatment with PTU, MMI and GSH prior to irradiation significantly increased the surviving cell fraction (SF) at 2 Gy (P , 0.05), while no effect was observed with KClO4. An increase in extracellular levels of cAMP was found only in PTU treated cells in a dose and timedependent manner. Cells incubated with agents that stimulate cAMP (forskolin and dibutyril cAMP) mimicked the effect of PTU on SF. Moreover, pretreatment with the inhibitor of protein kinase A, H-89, abolished the radioprotective effect of PTU. PTU treatment diminished radiation-induced apoptosis and protected cells against radiation-induced ROS elevation and suppression of the antioxidant enzyme?s activity. PTU was found to radioprotect normal thyroid cells through cAMP elevation and reduction in both apoptosis and radiation-induced oxidative stress damage.Fil: Perona, Marina. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (centro Atómico Constituyentes); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Dagrosa, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); ArgentinaFil: Pagotto, Romina María del Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Casal, Mariana. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncologí­a "Angel H. Roffo"; ArgentinaFil: Pignataro, Omar Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Pisarev, Mario Alberto. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Juvenal, Guillermo Juan. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (centro Atómico Constituyentes); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaRadiation Research Soc2012-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/9010Perona, Marina; Dagrosa, Maria Alejandra; Pagotto, Romina María del Luján; Casal, Mariana; Pignataro, Omar Pedro; et al.; Protection against radiation-induced damage of 6-propyl-2-thiouracil (PTU) in thyroid cells; Radiation Research Soc; Radiation Research; 179; 3; 11-2012; 352-3600033-7587enginfo:eu-repo/semantics/altIdentifier/url/http://www.rrjournal.org/doi/abs/10.1667/RR2658.1?code=rrs-site&journalCode=rareinfo:eu-repo/semantics/altIdentifier/doi/10.1667/RR2658.1info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:26:38Zoai:ri.conicet.gov.ar:11336/9010instacron: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 10:26:39.173CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Protection against radiation-induced damage of 6-propyl-2-thiouracil (PTU) in thyroid cells
title Protection against radiation-induced damage of 6-propyl-2-thiouracil (PTU) in thyroid cells
spellingShingle Protection against radiation-induced damage of 6-propyl-2-thiouracil (PTU) in thyroid cells
Perona, Marina
Radioprotector
Thyroid
Propylthiouracil
Cancer
Camp
title_short Protection against radiation-induced damage of 6-propyl-2-thiouracil (PTU) in thyroid cells
title_full Protection against radiation-induced damage of 6-propyl-2-thiouracil (PTU) in thyroid cells
title_fullStr Protection against radiation-induced damage of 6-propyl-2-thiouracil (PTU) in thyroid cells
title_full_unstemmed Protection against radiation-induced damage of 6-propyl-2-thiouracil (PTU) in thyroid cells
title_sort Protection against radiation-induced damage of 6-propyl-2-thiouracil (PTU) in thyroid cells
dc.creator.none.fl_str_mv Perona, Marina
Dagrosa, Maria 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, Maria Alejandra
Pagotto, Romina María del Luján
Casal, Mariana
Pignataro, Omar Pedro
Pisarev, Mario Alberto
Juvenal, Guillermo Juan
author_role author
author2 Dagrosa, Maria 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 Radioprotector
Thyroid
Propylthiouracil
Cancer
Camp
topic Radioprotector
Thyroid
Propylthiouracil
Cancer
Camp
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Many epidemiologic studies have shown that the exposure to high external radiation doses increases thyroid neoplastic frequency, especially when given during childhood or adolescence. The use of radioprotective drugs may decrease the damage caused by radiation therapy and therefore could be useful to prevent the development of thyroid tumors. The aim of this study was to investigate the possible application of 6-propyl-2-thiouracil (PTU) as a radioprotector in the thyroid gland. Rat thyroid epithelial cells (FRTL-5) were exposed to different doses of g irradiation with or without the addition of PTU, methimazole (MMI), reduced glutathione (GSH) and perchlorate (KClO4). Radiation response was analyzed by clonogenic survival assay. Cyclic AMP (cAMP) levels were measured by radioimmunoassay (RIA). Apoptosis was quantified by nuclear cell morphology and caspase 3 activity assays. Intracellular reactive oxygen species (ROS) levels were measured using the fluorescent dye 20,70-dichlorofluorescein- diacetate. Catalase, superoxide dismutase and glutathione peroxidase activities were also determined. Pretreatment with PTU, MMI and GSH prior to irradiation significantly increased the surviving cell fraction (SF) at 2 Gy (P , 0.05), while no effect was observed with KClO4. An increase in extracellular levels of cAMP was found only in PTU treated cells in a dose and timedependent manner. Cells incubated with agents that stimulate cAMP (forskolin and dibutyril cAMP) mimicked the effect of PTU on SF. Moreover, pretreatment with the inhibitor of protein kinase A, H-89, abolished the radioprotective effect of PTU. PTU treatment diminished radiation-induced apoptosis and protected cells against radiation-induced ROS elevation and suppression of the antioxidant enzyme?s activity. PTU was found to radioprotect normal thyroid cells through cAMP elevation and reduction in both apoptosis and radiation-induced oxidative stress damage.
Fil: Perona, Marina. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (centro Atómico Constituyentes); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Dagrosa, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina
Fil: Pagotto, Romina María del Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Casal, Mariana. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncologí­a "Angel H. Roffo"; Argentina
Fil: Pignataro, Omar Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Pisarev, Mario Alberto. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Juvenal, Guillermo Juan. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (centro Atómico Constituyentes); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Many epidemiologic studies have shown that the exposure to high external radiation doses increases thyroid neoplastic frequency, especially when given during childhood or adolescence. The use of radioprotective drugs may decrease the damage caused by radiation therapy and therefore could be useful to prevent the development of thyroid tumors. The aim of this study was to investigate the possible application of 6-propyl-2-thiouracil (PTU) as a radioprotector in the thyroid gland. Rat thyroid epithelial cells (FRTL-5) were exposed to different doses of g irradiation with or without the addition of PTU, methimazole (MMI), reduced glutathione (GSH) and perchlorate (KClO4). Radiation response was analyzed by clonogenic survival assay. Cyclic AMP (cAMP) levels were measured by radioimmunoassay (RIA). Apoptosis was quantified by nuclear cell morphology and caspase 3 activity assays. Intracellular reactive oxygen species (ROS) levels were measured using the fluorescent dye 20,70-dichlorofluorescein- diacetate. Catalase, superoxide dismutase and glutathione peroxidase activities were also determined. Pretreatment with PTU, MMI and GSH prior to irradiation significantly increased the surviving cell fraction (SF) at 2 Gy (P , 0.05), while no effect was observed with KClO4. An increase in extracellular levels of cAMP was found only in PTU treated cells in a dose and timedependent manner. Cells incubated with agents that stimulate cAMP (forskolin and dibutyril cAMP) mimicked the effect of PTU on SF. Moreover, pretreatment with the inhibitor of protein kinase A, H-89, abolished the radioprotective effect of PTU. PTU treatment diminished radiation-induced apoptosis and protected cells against radiation-induced ROS elevation and suppression of the antioxidant enzyme?s activity. PTU was found to radioprotect normal thyroid cells through cAMP elevation and reduction in both apoptosis and radiation-induced oxidative stress damage.
publishDate 2012
dc.date.none.fl_str_mv 2012-11
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/11336/9010
Perona, Marina; Dagrosa, Maria Alejandra; Pagotto, Romina María del Luján; Casal, Mariana; Pignataro, Omar Pedro; et al.; Protection against radiation-induced damage of 6-propyl-2-thiouracil (PTU) in thyroid cells; Radiation Research Soc; Radiation Research; 179; 3; 11-2012; 352-360
0033-7587
url http://hdl.handle.net/11336/9010
identifier_str_mv Perona, Marina; Dagrosa, Maria Alejandra; Pagotto, Romina María del Luján; Casal, Mariana; Pignataro, Omar Pedro; et al.; Protection against radiation-induced damage of 6-propyl-2-thiouracil (PTU) in thyroid cells; Radiation Research Soc; Radiation Research; 179; 3; 11-2012; 352-360
0033-7587
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.rrjournal.org/doi/abs/10.1667/RR2658.1?code=rrs-site&journalCode=rare
info:eu-repo/semantics/altIdentifier/doi/10.1667/RR2658.1
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
application/pdf
dc.publisher.none.fl_str_mv Radiation Research Soc
publisher.none.fl_str_mv Radiation Research Soc
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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