Fundamental Toxicological Sciences

Paper Details

Fundamental Toxicological Sciences
Vol. 8 No. 7 December 31, 2021 p.249-260
Original Article
Low-dose ionizing radiation suppresses the apoptosis-induced by serum-removal culture
  • Yuki Nakamura (Division of Toxicology, Department of Pharmacology, Toxicology and Therapeutics, Showa University School of Pharmacy / nakamura91@pharm.showa-u.ac.jp)
Yuki Nakamura 1) , Shinsuke Katoh 2) , Junya Kobayashi 3) , Tomonobu Umeda 2) , Yoshiko Kobayashi 2) , Satoshi Numazawa 1)
1) Division of Toxicology, Department of Pharmacology, Toxicology and Therapeutics, Showa University School of Pharmacy , 2) Department of Radiation Science, Yokohama University of Pharmacy , 3) Department of Radiological Sciences, School of Health Sciences at Narita, International University of Health and Welfare
Keywords: Low-dose irradiation, Apoptosis, DNA damage repair, Stress response, PC12 cell
Abstracts

Low-dose ionizing radiation (LDIR) at a dose reported in the radiation hormesis effect and adaptive response enhances antioxidant abilities and DNA repair abilities. In this study, we investigated the effects of radiation at 0.1–3 Gy on apoptosis induced by serum removal. Irradiation of 1 Gy at the timing of apoptosis induction improved cell viability. The inhibitory effect on apoptosis was strongly observed at 1 Gy of radiation rather than 0.1 Gy, which is the dose reported in the radiation hormesis effect and adaptive response. To study the effect of irradiation on cell cycle and DNA damage repair system, we investigated the activation of cyclin A and the phosphorylation of KAP1, and results showed that the irradiation decreased cyclin A and activated KAP1, suggesting cell cycle arrest and the activation of DNA damage repair system after the irradiation. Next, we investigated the increased phosphorylation of p38 and Jun-N-terminal kinase (JNK), stress response factors, that occurs during the progression of apoptosis by serum removal, and results showed that 1 Gy of irradiation increased p38 but decreased JNK. We investigated the effect of the irradiation on the regulation of DUSP1, which is a substrate specificity for MAPK, and results showed that the irradiation maintained the expression level for the transient induction of DUSP1 expression by serum removal. The results suggest that in LDIR at 1 Gy, apoptosis was suppressed by the activation of DNA damage repair signaling and crosstalk signaling between the p38 and JNK pathways mediated by DUSP1 induction.