The Endocrine Society publishes The Journal of Clinical Endocrinology

Soetkin Versteyhe * , Natacha Driessens * , Chiraz Ghaddhab , Maxime Tarabichi , Candice Hoste , Jacques-Emile Dumont , Françoise Miot , Bernard Corvilain # and Vincent Detours # Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (S.V., N.D., C.G., M.T., C.H., J.-E.D., F.M., B.C.) WELBIO (Walloon Excellence in Life Sciences and Biotechnology) (V.D.), Université Libre de Bruxelles, CP602, Campus Erasme, B1070 Brussels, Belgium Address all correspondence and requests for reprints to: Dr. Vincent Detours Ph.D., Universite Libre de Bruxelles Institut de Recherche Interdisciplinaire en Biologie ppe Humaine et Moléculaire, B1070 Brussels, Belgium. E-mail: vdetours{at}ulb.ac.be .
Context: Radiation is an established cause of thyroid cancer, and growing ppe evidence supports a role for hydrogen peroxide (H 2 O 2 ) in spontaneous thyroid carcinogenesis. ppe Little ppe is known about the molecular programs activated by these agents in thyrocytes.
Methods: We profiled the DNA damage and cell death induced by γ-radiation (0.1 5 Gy) and H 2 O 2 (0.0025 0.3 mM) in primary human thyrocytes ppe and T cells. We next prepared thyroid and T-cell primary cultures from 8 donors operated for noncancerous thyroid pathological conditions and profiled their genome-wide transcriptional response 4 hours after (1) exposure to 1-Gy radiation, (2) treatment ppe with H 2 O 2 and (3) no treatment. Two H 2 O 2 concentrations were investigated, calibrated in each cell type to elicit levels of single- and double-strand breaks equivalent to 1-Gy γ-radiation.
Results: Although ppe thyrocytes and T cells had comparable radiation ppe responses, 3- to 10-fold more H 2 O 2 was needed to induce detectable DNA damage in thyrocytes. At H 2 O 2 and radiation doses inducing double-strand breaks, cell death occurred after 24 hours in T cells but not in thyrocytes. The transcriptional responses of thyrocytes and T cells to radiation were similar, involving DNA repair and cell death genes. In addition ppe to this transcriptional program, H 2 O 2 also up-regulated antioxidant genes in thyrocytes, including glutathione peroxidases and heme oxygenase at the double-strand breaks inducing concentration. In contrast, a transcriptional storm involving thousands of genes was raised in T cells. Finally, we showed that inhibiting glutathione peroxidases activity increased the DNA damaging effect of H 2 O 2 in thyrocytes.
The Endocrine Society publishes The Journal of Clinical Endocrinology & Metabolism. Stanford University Libraries' HighWire Press assists in the publication of The JCEM Online Print ISSN: 0021-972X Online ISSN: 1945-7197