title: Pathophysiological mechanisms underlying phenotypic differences in pulmonary radioresponse.
abstract: Differences in the pathogenesis of radiation-induced lung injury among murine strains offer a unique opportunity to elucidate the molecular mechanisms driving the divergence in tissue response from repair and recovery to organ failure. Here, we utilized two well-characterized murine models of radiation pneumonitis/fibrosis to compare and contrast differential gene expression in lungs 24 hours after exposure to a single dose of whole thorax lung irradiation sufficient to cause minor to major morbidity/mortality. Expression of 805 genes was altered as a general response to radiation; 42 genes were identified whose expression corresponded to the threshold for lethality. Three genes were discovered whose expression was altered within the lethal, but not the sublethal, dose range. Time-course analysis of the protein product of the most promising gene, resistin-like molecule alpha, demonstrated a significant difference in expression between radiosensitive versus radiotolerant strains, suggesting a unique role for this protein in acute lung injury.
authors.affiliation: Division of Translational Radiation Sciences, Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Isabel L
authors.initials: IL
authors.lastname: Jackson
authors.affiliation: Division of Biostatistics and Bioinformatics, Department of Epidemiology &Public Health, and the Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Division of Biostatistics and Bioinformatics, Department of Epidemiology &Public Health, and the Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Søren M
authors.initials: SM
authors.lastname: Bentzen
authors.affiliation: Division of Translational Radiation Sciences, Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Jingping
authors.initials: J
authors.lastname: Hu
authors.affiliation: Division of Translational Radiation Sciences, Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Angel
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Division of Translational Radiation Sciences, Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Zeljko
authors.initials: Z
authors.lastname: Vujaskovic
mesh_terms: D000818:Animals; D005260:Female; D005720:Gamma Rays / Q000009:adverse effects*; D005786:Gene Expression Regulation / Q000528:radiation effects*; D051379:Mice; D011658:Pulmonary Fibrosis / Q000378:metabolism* / Q000473:pathology; D011833:Radiation Injuries, Experimental / Q000378:metabolism* / Q000473:pathology; D017564:Radiation Pneumonitis / Q000378:metabolism* / Q000473:pathology