Title: Study of 6-propyl-2-thiouracil as a radioprotector for the thyroid gland

Authors: Marina Perona, Alejandra Dagrosa, Romina Pagotto, Mariana Casal, Omar Pignataro, Mario Pisarev, Guillermo Juvenal,

Addresses: Department of Radiobiology, Constituyentes Atomic Center, CNEA, General Paz 1499 C.P. 1650 San Martin, Buenos Aires, Argentina; National Council of Scientific and Technical Investigations (CONICET), Argentina. ' Department of Radiobiology, Constituyentes Atomic Center, CNEA, General Paz 1499 C.P. 1650 San Martin, Buenos Aires, Argentina; National Council of Scientific and Technical Investigations (CONICET), Argentina. ' Biological and Experimental Medicine Institute (IByME-CONICET), Vuelta de Obligado 2490 C.P.1428, Ciudad Autonoma de Buenos Aires, Argentina. ' Department of Radiobiology, Constituyentes Atomic Center, CNEA, General Paz 1499 C.P 1650 San Martin, Buenos Aires, Argentina; Oncological Institute ''Angel H. Roffo'', UBA, Avenida San Martin 5481, Ciudad Autonoma de Buenos Aires, Argentina. ' Biological and Experimental Medicine Institute (IByME-CONICET), Vuelta de Obligado 2490 C.P.1428, Ciudad Autonoma de Buenos Aires, Argentina. ' Department of Radiobiology, Constituyentes Atomic Center, CNEA, General Paz 1499 C.P 1650 San Martin, Buenos Aires, Argentina; Oncological Institute ''Angel H. Roffo'', UBA, Avenida San Martin 5481, Ciudad Autonoma de Buenos Aires, Argentina. ' Department of Radiobiology, Constituyentes Atomic Center, CNEA, General Paz 1499 C.P 1650 San Martin, Buenos Aires, Argentina; National Council of Scientific and Technical Investigations (CONICET), Argentina

Abstract: The objective of the paper was to study the application of 6-propyl-2-thiouracil (PTU) as a radioprotector for the thyroid gland. Rat thyroid epithelial cells (FRTL-5) and human colon cancer cells (ARO81-1) were exposed to γ-irradiation with or without 1 mM PTU. Radiation response was analysed by clonogenic survival assay. Cyclic AMP levels were measured by Radioimmunoassay (RIA). The results showed that PTU increased the Surviving Cell Fraction (SF) at 2 Gy significantly (p < 0.05) in both cell lines. PTU increased extracellular levels of cAMP in all the treatments in a dose- and time-dependent manner for FRTL-5 cells. In ARO81-1 cells, a peak was observed at 24 hours in extracellular levels incubated with 1 mM PTU (36.97 ± 6.74 fmol/μg prot vs. control: 17.53 ± 3.9 fmol/μg prot, p < 0.001). Forskolin and dibutyril cAMP mimicked the effect of PTU on SF. Thus PTU appears to be a radioprotector for thyroid cells and could exert its effect through cAMP.

Keywords: thyroid glands; PTU; low radiation; radioprotection; cyclic AMP; 6-propyl-2-thiouracil; rat thyroid epithelial cells; human colon cancer cells; gamma irradiation.

DOI: 10.1504/IJLR.2010.036962

International Journal of Low Radiation, 2010 Vol.7 No.5, pp.366 - 379

Published online: 18 Nov 2010 *

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