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Published in: Strahlentherapie und Onkologie 3/2012

01-03-2012 | Original article

Radiation-induced changes in breathing frequency and lung histology of C57BL/6J mice are time- and dose-dependent

Authors: T. Eldh, F. Heinzelmann, A. Velalakan, W. Budach, C. Belka, V. Jendrossek

Published in: Strahlentherapie und Onkologie | Issue 3/2012

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Abstract

Purpose

Pneumonitis and fibrosis constitute serious adverse effects of radiotherapy in the thoracic region. In this study, time-course and dose-dependence of clinically relevant parameters of radiation-induced lung injury in C57BL/6J mice were analyzed. A well-characterized disease model is necessary for the analysis of the cellular and molecular mechanisms using genetically modified mice.

Material and methods

C57BL/6J mice received single dose right hemithorax irradiation with 12.5 or 22.5 Gy. Body weight and breathing frequency were recorded as parameters for health impairment. Lung tissue was collected over 24 weeks for histological analysis.

Results

Hemithorax irradiation with 12.5 or 22.5 Gy induced biphasic breathing impairment with the first increase between days 7 and 70. Although breathing impairment was more pronounced in the 22.5 Gy group, it was accompanied in both dose groups by pneumonitis-associated histological changes. A second rise in breathing frequency ratios became visible starting on day 70 with a steady increase until day 210. Again, breathing was more strongly affected in the 22.5 Gy group. However, breathing impairment coincided only in the 22.5 Gy group with a significant increase in collagen deposition in the lung tissue by day 210. Tissue inflammation and fibrosis were observed in the irradiated and the shielded lungs, pointing toward involvement of systemic effects.

Conclusion

Hemithorax irradiation induces time-dependent pneumonitis and fibrosis in C57BL/6J mice. While hemithorax irradiation with 12.5 Gy is sufficient to induce lung inflammation, it is below the threshold for collagen deposition and fibrosis development by day 210.
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Metadata
Title
Radiation-induced changes in breathing frequency and lung histology of C57BL/6J mice are time- and dose-dependent
Authors
T. Eldh
F. Heinzelmann
A. Velalakan
W. Budach
C. Belka
V. Jendrossek
Publication date
01-03-2012
Publisher
Springer-Verlag
Published in
Strahlentherapie und Onkologie / Issue 3/2012
Print ISSN: 0179-7158
Electronic ISSN: 1439-099X
DOI
https://doi.org/10.1007/s00066-011-0046-3

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