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Published in: Radiation Oncology 1/2020

01-12-2020 | Magnetic Resonance Imaging | Research

Impact of mouse strain and sex when modeling radiation necrosis

Authors: Andrew J. Boria, Carlos J. Perez-Torres

Published in: Radiation Oncology | Issue 1/2020

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Abstract

Background

Murine models are among the most common type of preclinical animal models used to study the human condition, but a wide selection of different mice is currently in use with these differences potentially compromising study results and impairing the ability to reconcile interstudy results. Our goal was to determine how the strain and sex of the mice selection would affect the development of radiation necrosis in our murine model of radiation-induced cerebral necrosis.

Methods

We generated this model by using a preclinical irradiator to irradiate a sub-hemispheric portion of the brain of mice with single-fraction doses of 80 Gy. Eight possible combinations of mice made up of two different with two substrains each (BALB/cN, BALB/cJ, C57BL/6 N, and C57BL/6 J) and both sexes were irradiated in this study. Radiation necrosis development was tracked up to 8 weeks with a 7 T Bruker MRI utilizing T2-weighted and post-contrast T1-weighted imaging. MRI results were compared to and validated with the use of histology which utilized a scale from 0 to 3 in ascending order of damage.

Results

Both time post-irradiation and strain (BALB/c vs C57BL/6) were significant factors affecting radiation necrosis development. Sex was in general not a statistically significant parameter in terms of radiation necrosis development.

Conclusion

Mouse strain thus needs to be considered when evaluating the results of necrosis models. However, sex does not appear to be a variable needing major consideration.
Appendix
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Literature
1.
go back to reference Kumar AJ, Leeds NE, Fuller GN, Tassel PV, Maor MH, Sawaya RE, et al. Malignant Gliomas: MR imaging Spectrum of radiation therapy- and chemotherapy-induced necrosis of the brain after treatment. Radiology. 2000;217:377–84.CrossRef Kumar AJ, Leeds NE, Fuller GN, Tassel PV, Maor MH, Sawaya RE, et al. Malignant Gliomas: MR imaging Spectrum of radiation therapy- and chemotherapy-induced necrosis of the brain after treatment. Radiology. 2000;217:377–84.CrossRef
2.
go back to reference Bojaxhiu B, Ahlhelm F, Walser M, Placidi L, Kliebsch U, Mikroutsikos L, et al. Radiation necrosis and white matter lesions in pediatric patients with brain tumors treated with pencil beam scanning proton therapy. Int J Radiat Oncol Biol Phys. 2018;100:987–96.CrossRef Bojaxhiu B, Ahlhelm F, Walser M, Placidi L, Kliebsch U, Mikroutsikos L, et al. Radiation necrosis and white matter lesions in pediatric patients with brain tumors treated with pencil beam scanning proton therapy. Int J Radiat Oncol Biol Phys. 2018;100:987–96.CrossRef
3.
go back to reference Boria AJ, Perez-Torres CJ. Influence of dose uniformity when replicating a gamma knife mouse model of radiation necrosis with a preclinical irradiator. Radiat Res. 2019;191:352–9.CrossRef Boria AJ, Perez-Torres CJ. Influence of dose uniformity when replicating a gamma knife mouse model of radiation necrosis with a preclinical irradiator. Radiat Res. 2019;191:352–9.CrossRef
4.
go back to reference Boria AJ, Perez-Torres CJ. Minimal difference between fractionated and single-fraction exposure in a murine model of radiation necrosis. Radiat Oncol Lond Engl. 2019;14:144.CrossRef Boria AJ, Perez-Torres CJ. Minimal difference between fractionated and single-fraction exposure in a murine model of radiation necrosis. Radiat Oncol Lond Engl. 2019;14:144.CrossRef
5.
go back to reference Kondo N, Sakurai Y, Takata T, Takai N, Nakagawa Y, Tanaka H, et al. Localized radiation necrosis model in mouse brain using proton ion beams. Appl Radiat Isot. 2015;106:242–6.CrossRef Kondo N, Sakurai Y, Takata T, Takai N, Nakagawa Y, Tanaka H, et al. Localized radiation necrosis model in mouse brain using proton ion beams. Appl Radiat Isot. 2015;106:242–6.CrossRef
6.
go back to reference Moravan MJ, Olschowka JA, Williams JP, O’Banion MK. Cranial irradiation leads to acute and persistent Neuroinflammation with delayed increases in T-cell infiltration and CD11c expression in C57BL/6 mouse brain. Radiat Res. 2011;176:459–73.CrossRef Moravan MJ, Olschowka JA, Williams JP, O’Banion MK. Cranial irradiation leads to acute and persistent Neuroinflammation with delayed increases in T-cell infiltration and CD11c expression in C57BL/6 mouse brain. Radiat Res. 2011;176:459–73.CrossRef
7.
go back to reference Grahn D, Hamilton KF. Genetic variation in the acute lethal response of four inbred mouse strains to whole body X-irradiation. Genetics. 1957;42:189–98.PubMedPubMedCentral Grahn D, Hamilton KF. Genetic variation in the acute lethal response of four inbred mouse strains to whole body X-irradiation. Genetics. 1957;42:189–98.PubMedPubMedCentral
8.
go back to reference Hanson WR, Fry RJ, Sallese AR, Frischer H, Ahmad T, Ainsworth EJ. Comparison of intestine and bone marrow radiosensitivity of the BALB/c and the C57BL/6 mouse strains and their B6CF1 offspring. Radiat Res. 1987;110:340–52.CrossRef Hanson WR, Fry RJ, Sallese AR, Frischer H, Ahmad T, Ainsworth EJ. Comparison of intestine and bone marrow radiosensitivity of the BALB/c and the C57BL/6 mouse strains and their B6CF1 offspring. Radiat Res. 1987;110:340–52.CrossRef
9.
go back to reference Okayasu R, Suetomi K, Yu Y, Silver A, Bedford JS, Cox R, et al. A deficiency in DNA repair and DNA-PKcs expression in the radiosensitive BALB/c mouse. Cancer Res. 2000;60:4342–5.PubMed Okayasu R, Suetomi K, Yu Y, Silver A, Bedford JS, Cox R, et al. A deficiency in DNA repair and DNA-PKcs expression in the radiosensitive BALB/c mouse. Cancer Res. 2000;60:4342–5.PubMed
10.
go back to reference Perincheri S, Dingle RWC, Peterson ML, Spear BT. Hereditary persistence of α-fetoprotein and H19 expression in liver of BALB/cJ mice is due to a retrovirus insertion in the Zhx2 gene. Proc Natl Acad Sci U S A. 2005;102:396–401.CrossRef Perincheri S, Dingle RWC, Peterson ML, Spear BT. Hereditary persistence of α-fetoprotein and H19 expression in liver of BALB/cJ mice is due to a retrovirus insertion in the Zhx2 gene. Proc Natl Acad Sci U S A. 2005;102:396–401.CrossRef
11.
go back to reference Ronchi JA, Figueira TR, Ravagnani FG, Oliveira HCF, Vercesi AE, Castilho RF. A spontaneous mutation in the nicotinamide nucleotide transhydrogenase gene of C57BL/6J mice results in mitochondrial redox abnormalities. Free Radic Biol Med. 2013;63:446–56.CrossRef Ronchi JA, Figueira TR, Ravagnani FG, Oliveira HCF, Vercesi AE, Castilho RF. A spontaneous mutation in the nicotinamide nucleotide transhydrogenase gene of C57BL/6J mice results in mitochondrial redox abnormalities. Free Radic Biol Med. 2013;63:446–56.CrossRef
12.
go back to reference Constanzo J, Masson-Côté L, Tremblay L, Fouquet JP, Sarret P, Geha S, et al. Understanding the continuum of radionecrosis and vascular disorders in the brain following gamma knife irradiation: an MRI study. Magn Reson Med. 2017;78:1420–31.CrossRef Constanzo J, Masson-Côté L, Tremblay L, Fouquet JP, Sarret P, Geha S, et al. Understanding the continuum of radionecrosis and vascular disorders in the brain following gamma knife irradiation: an MRI study. Magn Reson Med. 2017;78:1420–31.CrossRef
13.
go back to reference Belliveau J-G, Jensen MD, Stewart JMP, Solovey I, Klassen LM, Bauman GS, et al. Prediction of radiation necrosis in a rodent model using magnetic resonance imaging apparent transverse relaxation. Phys Med Biol. 2018;63:035010.CrossRef Belliveau J-G, Jensen MD, Stewart JMP, Solovey I, Klassen LM, Bauman GS, et al. Prediction of radiation necrosis in a rodent model using magnetic resonance imaging apparent transverse relaxation. Phys Med Biol. 2018;63:035010.CrossRef
14.
go back to reference Perez-Torres CJ, Engelbach JA, Cates J, Thotala D, Yuan L, Schmidt RE, et al. Toward distinguishing recurrent tumor from radiation necrosis: DWI and MTC in a gamma knife–irradiated mouse Glioma model. Int J Radiat Oncol. 2014;90:446–53.CrossRef Perez-Torres CJ, Engelbach JA, Cates J, Thotala D, Yuan L, Schmidt RE, et al. Toward distinguishing recurrent tumor from radiation necrosis: DWI and MTC in a gamma knife–irradiated mouse Glioma model. Int J Radiat Oncol. 2014;90:446–53.CrossRef
Metadata
Title
Impact of mouse strain and sex when modeling radiation necrosis
Authors
Andrew J. Boria
Carlos J. Perez-Torres
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2020
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/s13014-020-01585-5

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