Host: The Japan Radiation Research Society, Chairman of the 52nd Annual Meeting, Toshiteru Okubo (Radiation Effects Research Foundation)
The incidence of thyroid cancer is increased among the A-bomb survivors and people suffered from the Chernobyl Nuclear Power Plant Reactor accident. However, the precious molecular mechanisms underlying radiation-induced thyroid carcinogenesis are still unknown. In this study, we investigated DNA damaged response in primary human thyroid cells in vitro. Firstly, to investigate the induction of DNA damage checkpoint in response to 1.0 Gy of gamma-rays, we analyzed the number of Ser1981-phosphorylated ataxia–telangiectasia mutated (ATM) and 53BP1 foci by immunofluorescent staining. The number of 53BP1 foci was increased immediately after irradiation and reached a peak at 30 minutes. Almost all of the 53BP1 foci were co-localized with Ser1981-phosphorylated ATM foci. Most initial foci were disappeared within 24 hours after irradiation, while some foci were remained. Secondary, primary human thyroid cells were irradiated with 6 Gy of gamma rays, and cell cycle arrest was examined. We found that they showed permanent cell cycle arrest and exhibited morphology of senescent cells together with the expression of senescence-associated-β-galactosidase (SA-β-gal). In conclusion, our results demonstrated, for the first time, that primary human thyroid cells retain efficient DNA damage response as well as efficient DNA repair capacity. The cells harboring irreparable DNA damage undergo premature senescence to maintain the integrity of the genome, which could be the major defense mechanisms against ionizing radiation.
