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

Abstract

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.

• Authors: Marina Perona, María A Dagrosa, Romina Pagotto, Mariana Casal, Omar P Pignataro, Mario A Pisarev, Guillermo J Juvenal
• Journal: Radiation research (Radiat Res) Vol. 179 Issue 3 Pg. 352-60 (Mar 2013) ISSN: 1938-5404 [Electronic] United States
• PMID: 23398355 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Radiation-Protective Agents
• Reactive Oxygen Species
• Propylthiouracil
• Cyclic AMP
• Caspase 3

Topics

• Animals
• Caspase 3 (metabolism)
• Cell Line
• Cyclic AMP (metabolism)
• Oxidative Stress (drug effects)
• Propylthiouracil (pharmacology)
• Radiation-Protective Agents (pharmacology)
• Radioimmunoassay
• Rats
• Rats, Inbred F344
• Reactive Oxygen Species (metabolism)
• Thyroid Gland (drug effects, metabolism, radiation effects)