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The protective effect of stable iodide against radiation on thyroid cells was investigated. One physiological effect of stable iodine is well-rooted: stable iodine leads to a reduced thyroid uptake of radioactive iodine. This work wants to focus on an intrinsic effect of stable iodine by which DNA-damage in cells is prevented. To investigate this intrinsic effect thyroid cells (FRTL-5) were externally irradiated by use of a linear accelerator (LINAC) applying energy doses of 0.01 Gy-400 Gy and by incubation with various activity concentrations of 131 I (0.1-50 MBq/ml for 24 h). We added stable iodine (NaI) to the cells prior to external irradiation and investigated the effect of the concentration of stable iodine (1, 5, 15 μg/ml). In order to clarify whether thyroid cells have a distinctive and iodine-dependent reaction to ionizing radiation, keratinocytes (HaCaT) without NIS were exposed in the same way. As indicators for the cellular reaction, the extent of DNA fragmentation was determined (Roche, Mannheim, Germany). Both cell types showed distinct ability for apoptosis as proven with camptothecin. The addition of "cold" iodine from 1 to 15 μg/ml without irradiation ("negative control") did not change the response in both cell types. Plausibly, the radio-sensitivity of both cell types did increase markedly with increasing radiation dose but the radiation effect is diminished if iodine is added to the thyroid cells beforehand. The DNA-damage in thyroid cells after addition of cold iodine is reduced by a factor of 2-3. The skin cells did not show an significant change of radio-sensitivity depending on the presence of cold iodine. Elementary iodine possibly acts as a radical scavenger and thus markedly reduces the secondary radiation damage caused by the formation of cytotoxic radicals. This intrinsic radioprotective effect of iodine is seen only in cells with NIS., (Copyright © 2016 Elsevier Ltd. All rights reserved.)