Study of the 6-propyl-2-thiouracil (PTU) as a Radioprotector for the Thyroid Gland

PERONA, M; DAGROSA, MA; PAGOTTO, R; CASAL, M; PIGNATARO, O; PISAREV, M A; JUVENAL, GJ

Chicago, USA

Congreso; Annual Meeting of the American Thyroid Association; 2008

American Thyroid Association

Introduction: Many epidemiologic studies have shown that the exposition to high external radiation doses increase thyroid neoplastic frequency, especially when given during childhood or adolescence. The use of radioprotectors, drugs that protect cells from the damage caused by radiation therapy, could be useful to prevent the development of thyroid tumors in patients treated with this therapy. Objetive: Study of propylthiouracil as a radioprotector in the thyroid gland. Methods: FRTL-5 and ARO cells were exposed to ã-irradiation at different doses (1 to 8 Gy) in the presence or absence of PTU (1mM). Cell surviving fractions (SF) were determined by the standard in vitro colony formation assay. o Clonogenic survival assay was performed and the survival fraction (SF) was used as an indicator of radiation effect on cells. Results: The SF was increased, in the presence of PTU, with all the doses in both cell lines. The ratio PTU vs control was about 2.7 and 2.3 for FRTL-5 and ARO cells respectively. Since it has been demonstrated that the increase of the radioresistence can be induced by the stimulation of the cAMP transduction signal pathway, cAMP levels were measured after incubating the cellular lines during 5, 24, 48 and 72 hours with different concentrations of PTU (0; 0,1 mM; 1 mM and 2 mM). PTU increased intra and extra cellular levels of cAMP in all the treatments. A peak was observed at 24 hs in extracelullar levels incubated with PTU 1 mM (36.97 ± 6.37 fmol/µg prot vs control: 16.67 ± 3.92 fmol/µg prot). Forskolin or dibutyril cAMP mimicked the effect of PTU on SF (0.881 ± 0.065 vs 0.398 ± 0.018 control, at 1Gy, 0.086 ± 0.01 vs 0.056 ± 0.003 at 5 Gy). Conclusion: PTU is a radioprotector for thyroid cells and exerts its effect through cAMP.