title: Role of H2O2 in RET/PTC1 chromosomal rearrangement produced by ionizing radiation in human thyroid cells.
abstract: During childhood, the thyroid gland is one of the most sensitive organs to the carcinogenetic effects of ionizing radiation that may lead to papillary thyroid carcinoma (PTC) associated with RET/PTC oncogene rearrangement. Exposure to ionizing radiation induces a transient "oxidative burst" through radiolysis of water, which can cause DNA damage and mediates part of the radiation effects. H(2)O(2) is a potent DNA-damaging agent that induces DNA double-strand breaks, and consequently, chromosomal aberrations. Irradiation by 5 Gy X-ray increased extracellular H(2)O(2). Therefore, we investigated the implication of H(2)O(2) in the generation of RET/PTC1 rearrangement after X-ray exposure. We developed a highly specific and sensitive nested reverse transcription-PCR method. By using the human thyroid cell line HTori-3, previously found to produce RET/PTC1 after gamma-irradiation, we showed that H(2)O(2), generated during a 5 Gy X-ray irradiation, causes DNA double-strand breaks and contributes to RET/PTC1 formation. Pretreatment of cells with catalase, a scavenger of H(2)O(2), significantly decreased RET/PTC1 rearrangement formation. Finally, RET/PTC chromosomal rearrangement was detected in HTori-3.1 cells after exposure of cells to H(2)O(2) (25 micromol/L), at a dose that did not affect the cell viability. This study shows for the first time that H(2)O(2) is able to cause RET/PTC1 rearrangement in thyroid cells and consequently highlights that oxidative stress could be responsible for the occurrence of RET/PTC1 rearrangement found in thyroid lesions even in the absence of radiation exposure.
authors.affiliation: UBRM, Centre National de l'Energie, des Sciences et des Techniques Nucléaires, Rabat, Morocco.
authors.forename: Rabii
authors.initials: R
authors.lastname: Ameziane-El-Hassani
authors.forename: Myriem
authors.initials: M
authors.lastname: Boufraqech
authors.forename: Odile
authors.initials: O
authors.lastname: Lagente-Chevallier
authors.forename: Urbain
authors.initials: U
authors.lastname: Weyemi
authors.forename: Monique
authors.initials: M
authors.lastname: Talbot
authors.forename: Didier
authors.initials: D
authors.lastname: Métivier
authors.forename: Françoise
authors.initials: F
authors.lastname: Courtin
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Bidart
authors.forename: Mohammed
authors.initials: M
authors.lastname: El Mzibri
authors.forename: Martin
authors.initials: M
authors.lastname: Schlumberger
authors.forename: Corinne
authors.initials: C
authors.lastname: Dupuy
mesh_terms: D015153:Blotting, Western; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D015321:Gene Rearrangement / Q000187:drug effects / Q000528:radiation effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014965:X-Rays
chemical_list: D015514:Oncogene Proteins, Fusion; D016877:Oxidants; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D011505:Protein-Tyrosine Kinases; C093573:ret-PTC fusion oncoproteins, human