Low dose irradiation of thyroid cells reveals a unique transcriptomic and epigenetic signature in RET/PTC-positive cells

Khalil Abou-El-Ardat, Pieter Monsieurs, Natasa Anastasov, Mike Atkinson, Hanane Derradji, Tim De Meyer, Sofie Bekaert, Wim Van Criekinge, Sarah Baatout

Research output: Contribution to journalA1: Web of Science-article

Abstract

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 4 Gy) 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 4 Gy in both RET/PTC-positive systems but no common genes at 62.5 mGy. 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. (C) 2011 Elsevier By. All rights reserved.

Original languageEnglish
JournalMutation Research
Volume731
Issue number1-2
Pages (from-to)27-40
Number of pages14
ISSN0027-5107
DOIs
Publication statusPublished - 1-Mar-2012
Externally publishedYes

Keywords

  • RET/PTC translocation
  • Thyroid
  • Micro RNA
  • X-irradiation, Low doses
  • MACROPHAGE INHIBITORY CYTOKINE-1
  • PERIPHERAL-BLOOD LYMPHOCYTES
  • RECEPTOR TYROSINE KINASE
  • IONIZING-RADIATION
  • GENE-EXPRESSION
  • TUMOR-SUPPRESSOR
  • PAPILLARY CARCINOMAS
  • HUMAN FIBROBLASTS
  • TRANSGENIC MICE
  • POST-CHERNOBYL

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