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

Authors
Perona, Marina; Dagrosa, María Alejandra; Pagotto, Romina María del Luján; Casal, Mariana; Pignataro, Omar Pedro; Pisarev, Mario Alberto; Juvenal, Guillermo Juan
Publication Year
2014
Language
English
Format
article
Status
Published version
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.
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
Subject
COLON CANCER
IONIZING RADIATION
PROPYLTHIOURACIL
RADIOPROTECTION
THYROID
Otras Ciencias Biológicas
Ciencias Biológicas
CIENCIAS NATURALES Y EXACTAS
Access level
Restricted access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/76553