{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T07:31:26Z","timestamp":1793431886572,"version":"4.5.0"},"reference-count":46,"publisher":"Radiation Research Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Radiation Research"],"published-print":{"date-parts":[[2022,8,30]]},"abstract":"<jats:p>Lung is one of the high-risk organs for radiation-induced carcinogenesis, but the risk of secondary lung-cancer development after particle-beam therapy and the underlying mechanism(s) remain to be elucidated. To investigate the effects of particle-beam radiation on adjacent normal tissues during cancer therapy, 7-week-old male and female B6C3F1 mice were irradiated with 0.2\u20134 Gy of gamma rays (for comparison), carbon ions (290 MeV\/u, linear energy transfer 13 keV\/\u00b5m), or fast neutrons (0.05\u20131 Gy, mean energy, \u223c2 MeV), and lung-tumor development was assessed by histopathology. Mice irradiated with \u22652 Gy of carbon ions or \u22650.2 Gy of neutrons developed lung adenocarcinoma (AC) significantly sooner than did non-irradiated mice. The relative biological effectiveness values for carbon ions for lung AC development were 1.07 for male mice and 2.59 for females, and the corresponding values for neutrons were 4.63 and 4.57. Genomic analysis of lung ACs revealed alterations in genes involved in Egfr signaling. Hyperphosphorylation of Erk and a frequent nuclear abnormality (i.e., nuclear groove) were observed in lung ACs of mice irradiated with carbon ions or neutrons compared with ACs from non-irradiated or gamma-ray-irradiated groups. Our data indicate that the induction of lung AC by carbon ions occurred at a rate similar to that for gamma rays in males and approximately 2-to 3-fold greater than that for gamma rays in females. In contrast, the effect of neutrons on lung AC development was approximately 4- to 5-fold greater than that of gamma rays. Our results provide valuable information concerning risk assessment of radiation-induced lung tumors after particle-beam therapy and increase our understanding of the molecular basis of tumor development.<\/jats:p>","DOI":"10.1667\/rade-21-00192.1","type":"journal-article","created":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T11:10:55Z","timestamp":1662030655000},"page":"475-487","source":"Crossref","is-referenced-by-count":13,"title":["Lung-Cancer Risk in Mice after Exposure to Gamma Rays, Carbon Ions or Neutrons: Egfr Pathway Activation and Frequent Nuclear Abnormality"],"prefix":"10.1667","volume":"198","author":[{"given":"Kenshi","family":"Suzuki","sequence":"first","affiliation":[{"name":"Department of Radiation Effects Research, National Institute of Radiological Sciences (NIRS), National Institutes for Quantum Science and Technology (QST), Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunsuke","family":"Yamazaki","sequence":"additional","affiliation":[{"name":"Department of Radiation Effects Research, National Institute of Radiological Sciences (NIRS), National Institutes for Quantum Science and Technology (QST), Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken-ichi","family":"Iwata","sequence":"additional","affiliation":[{"name":"Department of Radiation Effects Research, National Institute of Radiological Sciences (NIRS), National Institutes for Quantum Science and Technology (QST), Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Radiation Effects Research, National Institute of Radiological Sciences (NIRS), National Institutes for Quantum Science and Technology (QST), Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takamitsu","family":"Morioka","sequence":"additional","affiliation":[{"name":"Department of Radiation Effects Research, National Institute of Radiological Sciences (NIRS), National Institutes for Quantum Science and Technology (QST), Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Daino","sequence":"additional","affiliation":[{"name":"Department of Radiation Effects Research, National Institute of Radiological Sciences (NIRS), National Institutes for Quantum Science and Technology (QST), Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mutsumi","family":"Kaminishi","sequence":"additional","affiliation":[{"name":"Department of Radiation Effects Research, National Institute of Radiological Sciences (NIRS), National Institutes for Quantum Science and Technology (QST), Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Radiation Effects Research, National Institute of Radiological Sciences (NIRS), National Institutes for Quantum Science and Technology (QST), Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiya","family":"Shimada","sequence":"additional","affiliation":[{"name":"Department of Radiation Effects Research, National Institute of Radiological Sciences (NIRS), National Institutes for Quantum Science and Technology (QST), Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shizuko","family":"Kakinuma","sequence":"additional","affiliation":[{"name":"Department of Radiation Effects Research, National Institute of Radiological Sciences (NIRS), National Institutes for Quantum Science and Technology (QST), Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1243","reference":[{"key":"9","doi-asserted-by":"crossref","unstructured":"DL Preston, E Ron, S Tokuoka, et al.  \"Radiat Res.\"  168, \"Solid cancer incidence in atomic bomb survivors: 1958-1998.\" 1 (2007)","DOI":"10.1667\/RR0763.1"},{"key":"8","doi-asserted-by":"crossref","unstructured":"K Furukawa, DL Preston, S Lonn, et al.  \"Radiat Res.\"  174, \"Radiation and smoking effects on lung cancer incidence among atomic bomb survivors.\" 72 (2010)","DOI":"10.1667\/RR2083.1"},{"key":"1","doi-asserted-by":"crossref","unstructured":"D De Ruysscher, M Mark Lodge, B Jones, et al.  \"Radiother Oncol.\"  103, \"Charged particles in radiotherapy: a 5-year update of a systematic review.\" 5 (2012)","DOI":"10.1016\/j.radonc.2012.01.003"},{"key":"3","doi-asserted-by":"crossref","unstructured":"T Kanai, M Endo, S Minohara, et al.  \"Int J Radiat Oncol Biol Phys.\"  44, \"Biophysical characteristics of HIMAC clinical 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