title: Preferential induction of RET/PTC1 rearrangement by X-ray irradiation.
abstract: Ionizing radiation is a well known risk factor of thyroid cancer development, but the mechanism of radiation induced carcinogenesis is not clear. The RET/PTC oncogene, an activated form of the RET proto-oncogene, is frequently observed in papillary thyroid carcinoma (PTC); RET/PTC1, -2 and -3 are known to be the three major forms. High frequencies of RET/PTC rearrangements have been observed in radiation-associated PTC, such as those appearing post-Chernobyl or post-radiotherapy, but the rearrangement types differ between these two populations. We investigated whether a specific type of RET/PTC rearrangement was induced by X-rays in vivo and in vitro. In human normal thyroid tissues transplanted in scid mice, the RET/PTC1 rearrangement was predominantly detected throughout the observation period (up to 60 days) after X-ray exposure of 50 Gy. On the other hand, RET/PTC3 was detected only 7 days after X-irradiation, and no transcript of RET/PTC2 was detected. These results are supported by the results of an in vitro study. The RET/PTC1 rearrangement was preferentially induced in a dose-dependent manner by X-rays within a high dose range (10, 50 and 100 Gy) in four cell lines. On the other hand, RET/PTC3 was induced at a much lower frequency, and no induction of RET/PTC2 was observed. These results suggest that the preferential induction of the RET/PTC1 rearrangement may play an important role in the early steps of thyroid carcinogenesis induced by acute X-irradiation.
authors.affiliation: Department of Radiobiology, Radiation Effects Research Foundation, Hiroshima, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Mizuno
authors.forename: K S
authors.initials: KS
authors.lastname: Iwamoto
authors.forename: S
authors.initials: S
authors.lastname: Kyoizumi
authors.forename: H
authors.initials: H
authors.lastname: Nagamura
authors.forename: T
authors.initials: T
authors.lastname: Shinohara
authors.forename: K
authors.initials: K
authors.lastname: Koyama
authors.forename: T
authors.initials: T
authors.lastname: Seyama
authors.forename: K
authors.initials: K
authors.lastname: Hamatani
mesh_terms: D000818:Animals; D002291:Carcinoma, Papillary / Q000209:etiology / Q000235:genetics*; D029721:Drosophila Proteins; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D015321:Gene Rearrangement; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009381:Neoplasms, Radiation-Induced / Q000209:etiology*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000209:etiology / Q000235:genetics*; D014407:Tumor Cells, Cultured; D014965:X-Rays
chemical_list: D029721:Drosophila Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; C494999:Ret protein, mouse; D016044:Fusion Proteins, bcr-abl