IN-VITRO IRRADIATION IS ABLE TO CAUSE RET ONCOGENE REARRANGEMENT

Elevated risk of thyroid cancers among the atomic bomb survivors as co mpared to the nonexposed population suggests that some genetic events related to thyroid cancer must be caused by ionizing radiation. Accord ingly, inducibility of RET oncogene rearrangements, i.e., the generati on of the RET-FTC oncogene, specific for thyroid cancer, was investiga ted among human undifferentiated thyroid carcinoma cells (8505C), whic h do not have RET oncogene rearrangement, after 0, 10, 50, and 1,00 Gy of in vitro X-irradiation by means of reverse transcription polymeras e chain reaction. After testing 10(8) cells at each dose point, 3 inde pendent samples obtained with 50 Gy of X-irradiation and 6 independent samples obtained with 100 Gy of X-irradiation showed a rearranged RET oncogene amplified band. No rearranged transcripts were obtained from cells irradiated with 0 or 10 Gy. All of the transcripts were sequenc ed and found to contain the D1OS170 and RET sequence. Interestingly, t wo types of rearrangements were included in these transcripts: one is specific for thyroid cancer and the other, which contains a 150-base p air insert, is atypical, not usually seen in vivo. This insert was fou nd to be the exon of D10S170. Furthermore, in fibrosarcoma cells (HT10 80), X-irradiation also induced RET oncogene rearrangements, which inc luded the same two types of rearrangements observed in the X-irradiate d thyroid cells (8505C). These results are in favor of the hypothesis that some radiation-induced thyroid cancers, including those among ato mic bomb survivors, might have developed when a growth advantage was o btained through a specific form of RET oncogene rearrangement induced by radiation exposure.