Low dose irradiation of thyroid cells reveals a unique transcriptomic and epigenetic signature in RET/PTC-positive cells.
The high doses of radiation received in the wake of the Chernobyl incident and the atomic bombing of Hiroshima and Nagasaki have been linked to the increased appearance of thyroid cancer in the children living in the vicinity of the site. However, the data gathered on the effect of low doses of radiation on the thyroid remain limited. We have examined the genome wide transcriptional response of a culture of TPC-1 human cell line of papillary thyroid carcinoma origin with a RET/PTC1 translocation to various doses (0.0625, 0.5, and 4Gy) of X-rays and compared it to response of thyroids with a RET/PTC3 translocation and against wild-type mouse thyroids irradiated with the same doses using Affymetrix microarrays. We have found considerable overlap at a high dose of 4Gy in both RET/PTC-positive systems but no common genes at 62.5mGy. In addition, the response of RET/PTC-positive system at all doses was distinct from the response of wild-type thyroids with both systems signaling down different pathways. Analysis of the response of microRNAs in TPC-1 cells revealed a radiation-responsive signature of microRNAs in addition to dose-responsive microRNAs. Our results point to the fact that a low dose of X-rays seems to have a significant proliferative effect on normal thyroids. This observation should be studied further as opposed to its effect on RET/PTC-positive thyroids which was subtle, anti-proliferative and system-dependent.
Centre d'Etude de l'Energie Nucléaire, Boeretang, Belgium. kabouela@sckcen.be
Khalil
K
Abou-El-Ardat
Pieter
P
Monsieurs
Nataša
N
Anastasov
Mike
M
Atkinson
Hanane
H
Derradji
Tim
T
De Meyer
Sofie
S
Bekaert
Wim
W
Van Criekinge
Sarah
S
Baatout
D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D004307:Dose-Response Relationship, Radiation; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D013961:Thyroid Gland / Q000528:radiation effects*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism; D014965:X-Rays
D035683:MicroRNAs; D015514:Oncogene Proteins, Fusion; D011505:Protein-Tyrosine Kinases; C093573:ret-PTC fusion oncoproteins, human