International journal of radiation biology · 2010
Radioprotection of thyroid cells mediated by methimazole.
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Kahmann Cindy, Wunderlich Gerd, Freudenberg Robert, Zöphel Klaus, Oehme Liane, Kotzerke Jörg
Аннотация
PURPOSE: The radioprotective effect of antithyroid drugs on radioiodine treatment is a controversial issue. However, it is of clinical relevance whether antithyroid medication has to be interrupted for therapy and when antithyroid medication can be continued after radioiodine treatment. We investigated DNA damage caused by internal or external radiation using thyroid cells (sodium iodine symporter [NIS] positive).
MATERIALS AND METHODS: Adherent thyroid cells were irradiated following incubation with the mediators methimazole and perchlorate using either X-ray tube or Re-188-perrhenate. DNA damage was quantified by OTM (Olive's tail moment) of the alkaline comet assay.
RESULTS: Following external irradiation of 15 Gy OTM was 4.3 ± 4.2 compared to 0.5 ± 1.4 in controls. DNA damage was reduced by methimazole to 70%. Incubation with Re-188 showed effects depending on presence of the mediators. Non-irradiated controls had a mean OTM < 1, internal irradiation increased OTM to 25.5 ± 9.1 in cells without mediators. OTM decreased to 60% after pre-incubation with methimazole and to 15% with perchlorate. Re-188 uptake was modified by both perchlorate and, to a lesser extent, methimazole.
CONCLUSIONS: Methimazole was shown to have a radioprotective effect not only by its scavenger capacity but also by interaction with NIS. Perchlorate acted by competitive inhibition of NIS mediated Re-188 uptake.
MATERIALS AND METHODS: Adherent thyroid cells were irradiated following incubation with the mediators methimazole and perchlorate using either X-ray tube or Re-188-perrhenate. DNA damage was quantified by OTM (Olive's tail moment) of the alkaline comet assay.
RESULTS: Following external irradiation of 15 Gy OTM was 4.3 ± 4.2 compared to 0.5 ± 1.4 in controls. DNA damage was reduced by methimazole to 70%. Incubation with Re-188 showed effects depending on presence of the mediators. Non-irradiated controls had a mean OTM < 1, internal irradiation increased OTM to 25.5 ± 9.1 in cells without mediators. OTM decreased to 60% after pre-incubation with methimazole and to 15% with perchlorate. Re-188 uptake was modified by both perchlorate and, to a lesser extent, methimazole.
CONCLUSIONS: Methimazole was shown to have a radioprotective effect not only by its scavenger capacity but also by interaction with NIS. Perchlorate acted by competitive inhibition of NIS mediated Re-188 uptake.