title: Basal levels of glutathione peroxidase correlate with onset of radiation induced lung disease in inbred mouse strains.
abstract: Biomarkers predicting for the radiation-induced lung responses of pneumonitis or fibrosis are largely unknown. Herein we investigated whether markers of oxidative stress and intracellular antioxidants, measured within days of radiation exposure, are correlated with the lung tissue injury response occurring weeks later. Mice of the eight inbred strains differing in their susceptibility to radiation-induced pulmonary fibrosis, and in the duration of asymptomatic survival, received 18 Gy whole thorax irradiation and were killed 6 h, 24 h, or 7 days later. Control mice were not irradiated. Lung levels of antioxidants superoxide dismutase, catalase, glutathione peroxidase (GPx), and glutathione, and of oxidative damage [reactive oxygen species (ROS) and 8-hydroxydeoxyguanosine (8-OHdG)], were biochemically determined. GPx was additionally measured through gene expression and immunohistochemical assessment of lung tissue, and activity in serum. ROS and 8-OHdG were increased postirradiation and exhibited significant strain and time-dependent variability, but were not strongly predictive of radiation-induced lung diseases. Antioxidant measures were not dramatically changed postirradiation and varied significantly among the strains. Basal GPx activity (r = 0.73, P = 0.04) in the lung and the pulmonary expression of GPx2 (r = 0.94, P = 0.0003) correlated with postirradiation asymptomatic survival, whereas serum GPx activity was inversely correlated (r = -0.80, P = 0.01) with fibrosis development. In conclusion, pulmonary oxidative stress and antioxidant markers were more affected by inbred strain than radiation over 7 days posttreatment. Lung GPx activity, and GPx2 expression, predicted for survival from lethal pneumonitis, and serum GPx for fibrosis, in this panel of mice.
authors.affiliation: Department of Human Genetics and the Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada; and.
authors.forename: Amit
authors.initials: A
authors.lastname: Kunwar
authors.affiliation: Department of Human Genetics and the Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada; and Department of Medicine and the Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada christina.haston@mcgill.ca.
authors.forename: Christina K
authors.initials: CK
authors.lastname: Haston
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D015153:Blotting, Western; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D051379:Mice; D008805:Mice, Inbred A; D008806:Mice, Inbred AKR; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018384:Oxidative Stress; D011658:Pulmonary Fibrosis / Q000175:diagnosis* / Q000201:enzymology / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D011829:Radiation Dosage; D017564:Radiation Pneumonitis / Q000175:diagnosis* / Q000201:enzymology / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D013909:Thorax / Q000528:radiation effects
chemical_list: D000975:Antioxidants; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D003849:Deoxyguanosine
keywords: fibrosis; pneumonitis; predictive biomarker; thoracic irradiation