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• W2057167453 abstract "Abstract Context: Radiation is an established cause of thyroid cancer, and growing evidence supports a role for hydrogen peroxide (H2O2) in spontaneous thyroid carcinogenesis. Little is known about the molecular programs activated by these agents in thyrocytes. Objective: The purpose of this study was to compare the responses of thyrocytes and T cells to H2O2 and radiation. Methods: We profiled the DNA damage and cell death induced by γ-radiation (0.1–5 Gy) and H2O2 (0.0025–0.3 mM) in primary human thyrocytes 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 with H2O2 and (3) no treatment. Two H2O2 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 thyrocytes and T cells had comparable radiation responses, 3- to 10-fold more H2O2 was needed to induce detectable DNA damage in thyrocytes. At H2O2 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 to this transcriptional program, H2O2 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 H2O2 in thyrocytes. Conclusion: We propose that high H2O2 production in thyrocytes is matched with specific transcriptionally regulated antioxidant protection." @default.
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• W2057167453 date "2013-10-01" @default.
• W2057167453 modified "2023-10-10" @default.
• W2057167453 title "Comparative Analysis of the Thyrocytes and T Cells: Responses to H2O2 and Radiation Reveals an H2O2-Induced Antioxidant Transcriptional Program in Thyrocytes" @default.
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• W2057167453 doi "https://doi.org/10.1210/jc.2013-1266" @default.
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