Preferential induction of RET/PTC1 rearrangement by X-ray irradiation.
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.
Mizuno
T
T
Department of Radiobiology, Radiation Effects Research Foundation, Hiroshima, Japan.
Iwamoto
K S
KS
Kyoizumi
S
S
Nagamura
H
H
Shinohara
T
T
Koyama
K
K
Seyama
T
T
Hamatani
K
K
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
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