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; JUVENAL, GJ

Rio de Janeiro, Brasil

Conferencia; 8th LOWRAD International Conference on "The Effects of Low and Very Low Doses of Ionizing Radiation on Human Health and Biotopes"; 2009

Comissao Nacional de Energia Nuclear, Brasil

Introduction: Many epidemiologic studies have shown that the exposition to the external radiation increases thyroid neoplastic frequency, especially when given during childhood or adolescence. Radioprotectors are chemicals agents that decrease the radiation damage. The mechanisms of radioprotection are complex. The application of a radioprotector drugs could be useful to avoid the development of malignancies in the normal areas after radiation treatment. Objective: Study of PTU as a radioprotector in the thyroid gland. Methods: Rat thyroid epithelial cells (FRTL-5) and human colon cancer cells (HT-29) 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 using the SF as an indicator of radiation effect on cells. Adenosine 3’,5’-cyclic-monophospate (cAMP) levels were measured by radioimmunoassay (RIA). Catalase activity was measured as described by Aebi. Results: The SF was increased, in the presence of PTU, with all the doses in both cell lines. The dose reduction factor (DRF) for 3 Gy equals 1.7 and 1.4 and 1.5 and 1.9 for 5 Gy in FRTL-5 and HT-29 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; 0.5 mM; 1 mM and 1.5 mM). PTU increased extra cellular levels of cAMP in all the treatments in a dose and time dependent manner for FRTL-5 cells. Meanwhile, a peak was observed at 24 hs in extra cellular levels incubated with PTU 1 mM (36.97 ± 6.74 fmol/µg prot vs control: 17.53 ± 3.9 fmol/µg prot, p<0.001) in HT-29  cells. Forskolin and dibutyril cAMP mimicked the effect of PTU on SF (0.469 ± 0.003 vs. 0.31 ± 0.01 and 0.31 ± 0.02 vs. 0.205 ± 0.03, at 3 and 5 Gy). One hour after the irradiation PTU increased catalase’s activity in both cell lines at 3 Gy and 5 Gy (p<0.05). Twenty four hours later, the activity was augmented at 3 and 5 Gy (p<0.05) for FRTL-5 cells. Conclusion: PTU is a radioprotector for thyroid cells and exerts its effect through cAMP and the enhancement of antioxidant enzyme’s activity.