title: Strain-dependent damage in mouse lung after carbon ion irradiation.
abstract: OBJECTIVE
  To examine whether inherent factors produce differences in lung morbidity in response to carbon ion (C-ion) irradiation, and to identify the molecules that have a key role in strain-dependent adverse effects in the lung.
  
  
  METHODS
  Three strains of female mice (C3H/He Slc, C57BL/6J Jms Slc, and A/J Jms Slc) were locally irradiated in the thorax with either C-ion beams (290 MeV/n, in 6 cm spread-out Bragg peak) or with ¹³⁷Cs γ-rays as a reference beam. We performed survival assays and histologic examination of the lung with hematoxylin-eosin and Masson's trichrome staining. In addition, we performed immunohistochemical staining for hyaluronic acid (HA), CD44, and Mac3 and assayed for gene expression.
  
  
  RESULTS
  The survival data in mice showed a between-strain variance after C-ion irradiation with 10 Gy. The median survival time of C3H/He was significantly shortened after C-ion irradiation at the higher dose of 12.5 Gy. Histologic examination revealed early-phase hemorrhagic pneumonitis in C3H/He and late-phase focal fibrotic lesions in C57BL/6J after C-ion irradiation with 10 Gy. Pleural effusion was apparent in C57BL/6J and A/J mice, 168 days after C-ion irradiation with 10 Gy. Microarray analysis of irradiated lung tissue in the three mouse strains identified differential expression changes in growth differentiation factor 15 (Gdf15), which regulates macrophage function, and hyaluronan synthase 1 (Has1), which plays a role in HA metabolism. Immunohistochemistry showed that the number of CD44-positive cells, a surrogate marker for HA accumulation, and Mac3-positive cells, a marker for macrophage infiltration in irradiated lung, varied significantly among the three mouse strains during the early phase.
  
  
  CONCLUSIONS
  This study demonstrated a strain-dependent differential response in mice to C-ion thoracic irradiation. Our findings identified candidate molecules that could be implicated in the between-strain variance to early hemorrhagic pneumonitis after C-ion irradiation.
authors.affiliation: Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Moritake
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Fujita
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Yanagisawa
authors.forename: Miyako
authors.initials: M
authors.lastname: Nakawatari
authors.forename: Kaori
authors.initials: K
authors.lastname: Imadome
authors.forename: Etsuko
authors.initials: E
authors.lastname: Nakamura
authors.forename: Mayumi
authors.initials: M
authors.lastname: Iwakawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Imai
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D002244:Carbon / Q000009:adverse effects*; D002588:Cesium Radioisotopes / Q000009:adverse effects; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D014453:Glucuronosyltransferase / Q000378:metabolism; D055436:Growth Differentiation Factor 15 / Q000378:metabolism; D018960:Hyaluronan Receptors / Q000378:metabolism; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000378:metabolism; D018499:Linear Energy Transfer; D008168:Lung / Q000737:chemistry / Q000378:metabolism / Q000528:radiation effects*; D051379:Mice; D008805:Mice, Inbred A; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010996:Pleural Effusion / Q000209:etiology / Q000473:pathology; D011833:Radiation Injuries, Experimental / Q000401:mortality; D017564:Radiation Pneumonitis / Q000473:pathology; D011836:Radiation Tolerance / Q000235:genetics*; D013045:Species Specificity; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D000943:Antigens, Differentiation; D002588:Cesium Radioisotopes; C526141:Gdf15 protein, mouse; D055436:Growth Differentiation Factor 15; D018960:Hyaluronan Receptors; C036763:monocyte-macrophage differentiation antigen; D002244:Carbon; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; D000076002:Hyaluronan Synthases