PMID- 30566388 OWN - NLM STAT- MEDLINE DCOM- 20190405 LR - 20190405 IS - 1938-5404 (Electronic) IS - 0033-7587 (Linking) VI - 191 IP - 2 DP - 2019 Feb TI - Dose-Dependent Increase of Nrf2 Target Gene Expression in Mice Exposed to Ionizing Radiation. PG - 176-188 LID - 10.1667/RR15203.1 [doi] AB - Nuclear factor-erythroid-2-related factor 2 transcription factor (Nrf2) is activated by reactive oxygen species (ROS) and binds to antioxidant response elements in the promoter regions of its target genes involved in redox regulation and antioxidative functions. In this study, we elucidated the relationship between radiation dose and the expression response of Nrf2 target genes involved in oxidative stress, such as heme oxygenase 1, ferritin heavy polypeptide 1 ( Fth1), NADPH dehydrogenase quinone 1, glutamate-cysteine ligase catalytic subunit, glutamate-cysteine ligase modifier subunit, glutathione reductase ( Gsr) and thioredoxin reductase 1 genes, in peripheral blood from X-ray irradiated mice. Whole-body radiation doses ranged from 0.5 to 3 Gy, and gene expressions were analyzed using reverse transcription quantitative polymerase chain reaction. A significant relationship was observed only for one gene: a statistically significant positive correlation between radiation dose and Fth1 mRNA expression was detected. However, Fth1 did not show any correlations with the biological damages induced by radiation tested in this study. Furthermore, while Gsr expression was significantly associated with spleen weight loss, splenic cell number reduction and bone marrow cell death apoptosis, no significant correlation was observed between Gsr expression and radiation dose. Together these results indicate that Nrf2 target gene expression is closely related to radiation dose and its level may reflect biological damages induced by ionizing radiation. These findings suggest the possibility for application of these target genes as a bio-dosimeter and/or damage marker in individuals exposed to ionizing radiation. FAU - Miura, Shuta AU - Miura S AD - a Department of Radiology, Akita Kousei Medical Center, Akita 011-0948, Japan. FAU - Yamaguchi, Masaru AU - Yamaguchi M AD - b Department of Radiation Science, Hirosaki University Graduate School of Health Sciences, Aomori 036-8564, Japan. FAU - Yoshino, Hironori AU - Yoshino H AD - b Department of Radiation Science, Hirosaki University Graduate School of Health Sciences, Aomori 036-8564, Japan. FAU - Nakai, Yuji AU - Nakai Y AD - c Institute for Food Sciences, Hirosaki University, Aomori 038-0012, Japan. FAU - Kashiwakura, Ikuo AU - Kashiwakura I AD - b Department of Radiation Science, Hirosaki University Graduate School of Health Sciences, Aomori 036-8564, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181219 PL - United States TA - Radiat Res JT - Radiation research JID - 0401245 RN - 0 (NF-E2-Related Factor 2) RN - 0 (Nfe2l2 protein, mouse) SB - IM MH - Animals MH - Bone Marrow Cells/radiation effects MH - Cell Death/radiation effects MH - Dose-Response Relationship, Radiation MH - Gene Expression Regulation/*radiation effects MH - Mice MH - NF-E2-Related Factor 2/*genetics MH - Organ Size/radiation effects MH - Oxidative Stress/genetics MH - *Radiation, Ionizing MH - Reverse Transcriptase Polymerase Chain Reaction MH - Spleen/radiation effects MH - Whole-Body Irradiation EDAT- 2018/12/20 06:00 MHDA- 2019/04/06 06:00 CRDT- 2018/12/20 06:00 PHST- 2018/12/20 06:00 [pubmed] PHST- 2019/04/06 06:00 [medline] PHST- 2018/12/20 06:00 [entrez] AID - 10.1667/RR15203.1 [pii] AID - 10.1667/RR15203.1 [doi] PST - ppublish SO - Radiat Res. 2019 Feb;191(2):176-188. doi: 10.1667/RR15203.1. Epub 2018 Dec 19.