title: Identification of radiation response genes and proteins from mouse pulmonary tissues after high-dose per fraction irradiation of limited lung volumes.
abstract: The molecular effects of focal exposure of limited lung volumes to high-dose per fraction irradiation (HDFR) such as stereotactic body radiotherapy (SBRT) have not been fully characterized. In this study, we used such an irradiation system and identified the genes and proteins after HDFR to mouse lung, similar to those associated with human therapy.
  
  
  
  High focal radiation (90 Gy) was applied to a 3-mm volume of the left lung of C57BL6 mice using a small-animal stereotactic irradiator. As well as histological examination for lungs, a cDNA micro array using irradiated lung tissues and a protein array of sera were performed until 4 weeks after irradiation, and radiation-responsive genes and proteins were identified. For comparison, the long-term effects (12 months) of 20 Gy radiation wide-field dose to the left lung were also investigated.
  
  
  
  The genes ermap, epb4.2, cd200r3 (up regulation) and krt15, hoxc4, gdf2, cst9, cidec, and bnc1 (down-regulation) and the proteins of AIF, laminin, bNOS, HSP27, β-amyloid (upregulation), and calponin (downregulation) were identified as being responsive to 90 Gy HDFR. The gdf2, cst9, and cidec genes also responded to 20 Gy, suggesting that they are universal responsive genes in irradiated lungs. No universal proteins were identified in both 90 Gy and 20 Gy. Calponin, which was downregulated in protein antibody array analysis, showed a similar pattern in microarray data, suggesting a possible HDFR responsive serum biomarker that reflects gene alteration of irradiated lung tissue. These genes and proteins also responded to the lower doses of 20 Gy and 50 Gy HDFR.
  
  
  
  These results suggest that identified candidate genes and proteins are HDFR-specifically expressed in lung damage induced by HDFR relevant to SBRT in humans.
authors.affiliation: a Graduate School of Pharmaceutical Sciences , Ewha Womans University , Seoul , Korea.
authors.forename: Hee
authors.initials: H
authors.lastname: Jin
authors.affiliation: a Graduate School of Pharmaceutical Sciences , Ewha Womans University , Seoul , Korea.
authors.forename: Seulgi
authors.initials: S
authors.lastname: Jeon
authors.affiliation: a Graduate School of Pharmaceutical Sciences , Ewha Womans University , Seoul , Korea.
authors.forename: Ga-Young
authors.initials: GY
authors.lastname: Kang
authors.affiliation: b Division of Radiation Effects , Korea Institute of Radiological & Medical Sciences , Seoul , Korea.
authors.forename: Hae-June
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: c Department of Radiation Oncology , Yonsei University Health System , Seoul , Korea.
authors.forename: Jaeho
authors.initials: J
authors.lastname: Cho
authors.affiliation: a Graduate School of Pharmaceutical Sciences , Ewha Womans University , Seoul , Korea.
authors.forename: Yun-Sil
authors.initials: YS
authors.lastname: Lee
mesh_terms: D000818:Animals; D004307:Dose-Response Relationship, Radiation; D005786:Gene Expression Regulation / Q000528:radiation effects*; D008168:Lung / Q000378:metabolism* / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020543:Proteome / Q000378:metabolism*; D000069473:Radiation Dose Hypofractionation; D017564:Radiation Pneumonitis / Q000209:etiology / Q000378:metabolism*; D016634:Radiosurgery / Q000009:adverse effects*
chemical_list: D020543:Proteome
keywords: High-dose per fraction irradiation; microarray; mouse lung; protein antibody array