title: Focal exposure of limited lung volumes to high-dose irradiation down-regulated organ development-related functions and up-regulated the immune response in mouse pulmonary tissues.
abstract: BACKGROUND
  Despite the emergence of stereotactic body radiotherapy (SBRT) for treatment of medically inoperable early-stage non-small-cell lung cancer patients, the molecular effects of focal exposure of limited lung volumes to high-dose radiation have not been fully characterized. This study was designed to identify molecular changes induced by focal high-dose irradiation using a mouse model of SBRT.
  
  
  RESULTS
  Central areas of the mouse left lung were focally-irradiated (3 mm in diameter) with a single high-dose of radiation (90 Gy). Temporal changes in gene expression in the irradiated and non-irradiated neighboring lung regions were analyzed by microarray. For comparison, the long-term effect (12 months) of 20 Gy radiation on a diffuse region of lung was also measured. The majority of genes were down-regulated in the focally-irradiated lung areas at 2 to 3 weeks after irradiation. This pattern of gene expression was clearly different than gene expression in the diffuse region of lungs exposed to low-dose radiation. Ontological and pathway analyses indicated these down-regulated genes were mainly associated with organ development. Although the number was small, genes that were up-regulated after focal irradiation were associated with immune-related functions. The temporal patterns of gene expression and the associated biological functions were also similar in non-irradiated neighboring lung regions, although statistical significance was greatly reduced when compared with those from focally-irradiated areas of the lung. From network analysis of temporally regulated genes, we identified inter-related modules associated with diverse functions, including organ development and the immune response, in both the focally-irradiated regions and non-irradiated neighboring lung regions.
  
  
  CONCLUSIONS
  Focal exposure of lung tissue to high-dose radiation induced expression of genes associated with organ development and the immune response. This pattern of gene expression was also observed in non-irradiated neighboring areas of lung tissue, indicating a global lung response to focal high-dose irradiation.
authors.affiliation: Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon, 305-811, Republic of Korea. buykim@kiom.re.kr.
authors.forename: Bu-Yeo
authors.initials: BY
authors.lastname: Kim
authors.affiliation: Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, 120-750, Korea. jinhee2848@hanmail.net.
authors.forename: Hee
authors.initials: H
authors.lastname: Jin
authors.affiliation: Division of Radiation Effects, Korea Institute of Radiological & Medical Sciences, Seoul, 139-706, Korea. yjlee8@kirams.re.kr.
authors.forename: Yoon-Jin
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, 120-750, Korea. gykang0313@naver.com.
authors.forename: Ga-Young
authors.initials: GY
authors.lastname: Kang
authors.affiliation: Department of Radiation Oncology, Severance Hospital, Yonsei University College of Medicine, Seoul, 120-752, Korea. jjhmd@yuhs.ac.
authors.forename: Jaeho
authors.initials: J
authors.lastname: Cho
authors.affiliation: Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, 120-750, Korea. yslee0425@ewha.ac.kr.
authors.forename: Yun-Sil
authors.initials: YS
authors.lastname: Lee
mesh_terms: D000818:Animals; D004307:Dose-Response Relationship, Radiation; D015536:Down-Regulation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000528:radiation effects*; D063990:Gene Ontology; D007109:Immunity / Q000235:genetics / Q000528:radiation effects; D008168:Lung / Q000254:growth & development / Q000276:immunology / Q000528:radiation effects*; D008297:Male; D051379:Mice; D011658:Pulmonary Fibrosis; D016634:Radiosurgery; D015854:Up-Regulation
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