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 γ 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 2′,7′-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 time-dependent 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.
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1 March 2013
Research Articles|
February 11 2013
Protection against Radiation-Induced Damage of 6-Propyl-2-thiouracil (PTU) in Thyroid Cells
Marina Perona;
Marina Perona
aDepartment of Radiobiology (CAC), National Atomic Energy Commission (CNEA),
bNational Research Council (CONICET),
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María A. Dagrosa;
María A. Dagrosa
aDepartment of Radiobiology (CAC), National Atomic Energy Commission (CNEA),
bNational Research Council (CONICET),
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Romina Pagotto;
Romina Pagotto
bNational Research Council (CONICET),
cBiological and Experimental Medicine Institute (IByME),
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Mariana Casal;
Mariana Casal
dInstitute of Oncology “Ángel H. Roffo”; and
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Omar P. Pignataro;
Omar P. Pignataro
bNational Research Council (CONICET),
cBiological and Experimental Medicine Institute (IByME),
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Mario A. Pisarev;
Mario A. Pisarev
aDepartment of Radiobiology (CAC), National Atomic Energy Commission (CNEA),
eUniversity of Buenos Aires, Department of Human Biochemistry, School of Medicine, Argentina
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Guillermo J. Juvenal
Guillermo J. Juvenal
1
aDepartment of Radiobiology (CAC), National Atomic Energy Commission (CNEA),
bNational Research Council (CONICET),
1Address for correspondence: Department of Radiobiology (CAC), Nuclear Biochemistry Division, National Atomic Energy Commission (CNEA); Av. Del Libertador 8250, Buenos Aires, 1429, Argentina; e-mail: juvenal@cnea.gov.ar.
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Radiat Res (2013) 179 (3): 352–360.
Article history
Received:
April 20 2011
Accepted:
November 12 2012
Citation
Marina Perona, María A. Dagrosa, Romina Pagotto, Mariana Casal, Omar P. Pignataro, Mario A. Pisarev, Guillermo J. Juvenal; Protection against Radiation-Induced Damage of 6-Propyl-2-thiouracil (PTU) in Thyroid Cells. Radiat Res 1 March 2013; 179 (3): 352–360. doi: https://doi.org/10.1667/RR2658.1
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