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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.

 Bu-Yeo Kim  ;  Hee Jin  ;  Yoon-Jin Lee  ;  Ga-Young Kang  ;  Jaeho Cho  ;  Yun-Sil Lee 
 BMC GENETICS, Vol.17(29) : 1-21, 2016 
Journal Title
Issue Date
Animals ; Dose-Response Relationship, Radiation ; Down-Regulation ; Gene Expression Profiling ; Gene Expression Regulation/radiation effects* ; Gene Ontology ; Immunity/genetics ; Immunity/radiation effects ; Lung/growth & development ; Lung/immunology ; Lung/radiation effects* ; Male ; Mice ; Pulmonary Fibrosis ; Radiosurgery ; Up-Regulation
Stereotactic body radiotherapy ; Focal radiation ; Microarray ; Organ development ; Immune response
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.
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1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
Yonsei Authors
Cho, Jae Ho(조재호) ORCID logo https://orcid.org/0000-0001-9966-5157
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