Radioprotection of thyroid cells mediated by methimazole.
OBJECTIVE
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).


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.
Kahmann
Cindy
C
Department of Nuclear Medicine, University Hospital, Technische Universität Dresden, Germany.
Wunderlich
Gerd
G
Freudenberg
Robert
R
Zöphel
Klaus
K
Oehme
Liane
L
Kotzerke
Jörg
J
D013956:Antithyroid Agents / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D008713:Methimazole / Q000494:pharmacology*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D011868:Radioisotopes; D012211:Rhenium / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*
D013956:Antithyroid Agents; D011837:Radiation-Protective Agents; D011868:Radioisotopes; D008713:Methimazole; D012211:Rhenium