Establishment and identification of C57BL/6 mouse model with radiation‐induced pulmonary fibrosis
Yuan Meng1, Men Yu2, Sun Xin1,3, Zhao Maoyuan1,4, Bao Dan5, Yang Xu1, Sun Shuang1, Bao Yongxing1, Ma Zeliang1, Liu Yunsong1, Hui Zhouguang2
1Department of Radiation Oncology, National Cancer Center / National Clinical Research Center for Cancer / Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; 2Department of VIP Medical Services, National Cancer Center / National Clinical Research Center for Cancer / Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; 3Department of Radiation Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; 4Lung Cancer Center, West China Hospital of Sichuan University, Chengdu 610041, China; 5Department of Radiology, National Cancer Center / National Clinical Research Center for Cancer / Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
Abstract:Objective To establish the mouse model with radiation‐induced pulmonary fibrosis, and to identify and analyze it from the aspects of function, imaging and pathology. Methods Thirty C57BL/6 mice were randomly divided into the control group, 16 Gy irradiation group and 20Gy irradiation group. The mice in the irradiation groups received a single 16 Gy or 20 Gy chest X‐ray irradiation, and underwent functional examination, imaging examination and pathological examination at 3 and 6 months after irradiation. Results At 6 months after irradiation, hair on the chest and back of the mice turned white and fell off, and the airway resistance was increased significantly. CT images showed extensive patch shadows and consolidation in the lung. Three dimensional reconstruction suggested that the lung of mice was distorted and deformed, and the volume was decreased significantly. Pathological examination confirmed that there was extensive pulmonary fibrosis. Conclusions Significant pulmonary fibrosis occurs after 6 months of chest irradiation in mice. The animal model of radiation‐induced pulmonary fibrosis in C57BL/6 mice was successfully established.
Yuan Meng,Men Yu,Sun Xin et al. Establishment and identification of C57BL/6 mouse model with radiation‐induced pulmonary fibrosis[J]. Chinese Journal of Radiation Oncology, 2022, 31(10): 928-932.
[1] Morgan GW, Breit SN.Radiation and the lung: a reevaluation of the mechanisms mediating pulmonary injury[J]. Int J Radiat Oncol Biol Phys, 1995,31(2):361-369. DOI: 10.1016/0360-3016(94)00477-3. [2] Tyldesley S, Boyd C, Schulze K, et al.Estimating the need for radiotherapy for lung cancer: an evidence-based, epidemiologic approach[J]. Int J Radiat Oncol Biol Phys, 2001,49(4):973-985. DOI: 10.1016/s0360-3016(00)01401-2. [3] Carver JR, Shapiro CL, Ng A, et al.American society of clinical oncology clinical evidence review on the ongoing care of adult cancer survivors: cardiac and pulmonary late effects[J]. J Clin Oncol, 2007,25(25):3991-4008. DOI: 10.1200/JCO.2007.10.9777. [4] Abid SH, Malhotra V, Perry MC.Radiation-induced and chemotherapy-induced pulmonary injury[J]. Curr Opin Oncol, 2001,13(4):242-248. DOI: 10.1097/00001622-200107000-00006. [5] Cella L, Liuzzi R, D'Avino V, et al. Pulmonary damage in Hodgkin's lymphoma patients treated with sequential chemo-radiotherapy: Predictors of radiation-induced lung injury[J]. Acta Oncol, 2014,53(5):613-619. DOI: 10.3109/0284186X.2013.850739. [6] 白蕴红,王德文,徐在海,等.纤维连接蛋白和层粘连蛋白在大鼠放射性肺损伤中的变化[J].中华放射医学与防护杂志, 1995,15(5) : 330-333. DOI: 10.3760/cma.j.issn.0254-5098. 1995.05.113. Bai YH, Wang DW, Xu ZH, et al.Changes of fibronectin and laminin in radiation pulmonary injury of rats[J]. Chin J Radiol Med Protec, 1995,15(5) : 330-333. DOI: 10.3760/cma.j.issn.0254-5098.1995.05.113. [7] Kong FM, Randall TH, Avraham E, et al. Non‐small cell lung cancer therapy‐related pulmonary toxicity: an update on radiation pneumonitis and fibrosis[J]. Semin Oncol, 2005,32(2 Suppl 3): 42‐54. DOI: 10.1053/j.seminoncol.2005.03.009. [8] Chen Z, Wu Z, Ning W.Advances in molecular mechanisms and treatment of radiation-induced pulmonary fibrosis[J]. Transl Oncol, 2019,12(1):162-169. DOI: 10.1016/j.tranon. 2018.09.009. [9] He Y, Thummuri D, Zheng G, et al.Cellular senescence and radiation-induced pulmonary fibrosis[J]. Transl Res, 2019,209:14-21. DOI: 10.1016/j.trsl.2019.03.006. [10] Jin H, Kang GY, Jeon S, et al. Identification of molecular signatures involved in radiation‐induced lung fibrosis[J]. J Mol Med (Berl), 2019,97(1): 37‐47. DOI: 10.1007/s00109-018-1715-9. [11] Groves AM, Johnston CJ, Williams JP, et al.Role of infiltrating monocytes in the development of radiation-induced pulmonary fibrosis[J]. Radiat Res, 2018,189(3):300-311. DOI: 10.1667/RR14874.1. [12] Williams JP, Johnston CJ, Finkelstein JN. Treatment for radiation‐induced pulmonary late effects: spoiled for choice or looking in the wrong direction?[J]. Curr Drug Targets, 2010,11(11): 1386‐1394. DOI: 10.2174/1389450111009011386. [13] Hanania AN, Mainwaring W, Ghebre YT, et al.Radiation- induced lung injury: assessment and management[J]. Chest, 2019,156(1):150-162. DOI: 10.1016/j.chest.2019.03.033. [14] Arroyo-Hernández M, Maldonado F, Lozano-Ruiz F, et al.Radiation-induced lung injury: current evidence[J]. BMC Pulm Med, 2021,21(1):9. DOI: 10.1186/s12890-020-01376-4. [15] Moore BB, Hogaboam CM. Murine models of pulmonary fibrosis[J]. Am J Physiol Lung Cell Mol Physiol, 2008, 294(2): L152‐160. DOI: 10.1152/ajplung.00313. [16] Franko AJ, Sharplin J, Ward WF, et al. Evidence for two patterns of inheritance of sensitivity to induction of lung fibrosis in mice by radiation, one of which involves two genes[J]. Radiat Res, 1996,146(1): 68‐74. [17] Sharplin J, Franko AJ.A quantitative histological study of strain-dependent differences in the effects of irradiation on mouse lung during the early phase[J]. Radiat Res, 1989,119(1):1-14. [18] Youssef M, De Sanctis JB, Shah J, et al.Age-dependent progression in lung pathophysiology can be prevented by restoring fatty acid and ceramide imbalance in cystic fibrosis[J]. Lung, 2020,198(3):459-469. DOI: 10.1007/s00408-020-00353-2. [19] LomaskM. Further exploration of the Penh parameter[J]. Exp Toxicol Pathol, 2006,57(Suppl 2): 13‐20. DOI: 10.1016/j.etp.2006.02.014.