Compartmental responses after thoracic irradiation of mice: Strain differences

Journal Article · Fri Jul 01 04:00:00 EDT 2005 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2005.02.037· OSTI ID:20698590

Chiang, C -S ^[1]; Liu, W -C ^[1]; Jung, S -M ^[2]; Chen, F -H ^[1]; Wu, C -R ^[3]; McBride, William H ^[4]; Lee, C -C ^[5]; Hong, J -H ^[6]

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1. Department of Atomic Science, National Tsing Hua University, Taiwan (China)
2. Department of Pathology, Chung Gung Memorial Hospital, Taiwan (China)
3. Department of Radiation Oncology, Chung Gung Memorial Hospital, Taiwan (China)
4. Department of Radiation Oncology, University of California-Los Angeles, Los Angeles, CA (United States)
5. Department of Medical Imaging and Radiological Science, Chang Gung University, Taiwan (China)
6. Department of Radiation Oncology, Chung Gung Memorial Hospital, Taiwan (China) and Department of Medical Imaging and Radiological Science, Chang Gung University, Taiwan (China)

Purpose: To examine and compare the molecular and cellular processes leading to radiation fibrosis and pneumonitis in C57BL/6J and C3H/HeN mice. Methods and Materials: At indicated times after various doses of thoracic irradiation, the cell populations obtained by bronchoalveolar lavage of C57BL/6J mice were differentially analyzed by cytology and assessed by RNase protection (RPA) assay for levels of cytokines and related genes. The molecular responses in bronchial alveolar lavage (BAL) populations were compared with those in whole lung of C57BL/6J mice and with those of C3H/HeN mice. The former strain develops late radiation fibrosis, whereas the latter develop subacute radiation pneumonitis. Results: In C57BL/6J mice, a decrease in the total number of BAL cells was found 1 week after 6, 12, or 20 Gy thoracic irradiation with a subsequent dose-dependent increase up to 6 months. After 12 and 20 Gy, large, foamy macrophages and multinucleated cells became evident in BAL at 3 weeks, only to disappear at 4 months and reappear at 6 months. This biphasic response was mirrored by changes expression of mRNA for proinflammatory cytokines and the Mac-1 macrophage-associated antigen. As with BAL, whole lung tissue also showed biphasic cytokine and Mac-1 mRNA responses, but there were striking temporal differences between the two compartments, with changes in whole lung tissue correlating better than BAL with the onset of fibrosis in this strain. The radiation-induced proinflammatory mRNA responses had strain-dependent and strain-independent components. Thoracic irradiation of C3H/HeN induced similar increases in tumor necrosis factor (TNF)-{alpha}, interleukin (IL)-1{alpha}/{beta}, and interferon (IFN)-{gamma} mRNA expression in lung as it did in C57BL/6J mice during the 'presymptom' phase at 1-2 months. However, immediately preceding and during the pneumonitic time period at 3-4 months, TNF-{alpha} and IL-1{alpha}/{beta} mRNAs were highly upregulated in C3H/HeN mice, which develop pneumonitis, but not in C57BL/6J mice, which do not. At the onset of radiation fibrosis in C57BL/6J mice (5-6 months), irradiated lungs had increased levels of IL-1{alpha}/{beta} and IFN-{gamma} mRNA expression, but the TNF-{alpha} response was, notably, still muted. Conclusions: The major molecular and cellular events in lungs of C57BL/6J and C3H/HeN mice, which develop late fibrosis and subacute pneumonitis after thoracic irradiation respectively, take place within the interstitium and are not reflected within BAL populations. The initial proinflammatory responses are similar in the two strains, but later responses reflect the latent time to lesion development. TNF-{alpha} expression at 3-4 months may be important in radiation-induced pneumonitis, and its downregulation is important in avoiding this radiation-induced complication.

• OSTI ID: 20698590
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 3 Vol. 62; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

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62 RADIOLOGY AND NUCLEAR MEDICINE
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CYTOLOGY
FIBROSIS
INTERFERON
IRRADIATION
LUNGS
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MAXIMUM ACCEPTABLE CONTAMINATION
MICE
PNEUMONITIS
RADIATION DOSES