Comparison of Intestine and Bone Marrow Radiosensitivity of the BALB/c and the C57BL/6 Mouse Strains and Their B6CF 1 Offspring

Hanson, Wayne R.; Fry, R.J.M.; Sallese, Anthony; Frischer, Henri; Ahmad, Tanveer; Ainsworth, E. J.

doi:10.2307/3577002

Cited by 36 publications

(27 citation statements)

References 8 publications

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“…Mouse strain differences in radiosensitivity and survival have been observed for over 50 years (Grahn and Hamilton 1956; Hanson et al 1987). These findings may represent innate differences, particularly in the immune response, but also the enteric flora population.…”

Section: Discussionmentioning

confidence: 99%

Acute Gastrointestinal Syndrome in High-Dose Irradiated Mice

Booth¹,

Tudor²,

Tudor³

et al. 2012

Health Physics

174

185

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The most detailed reports of the response of the gastrointestinal system to high dose acute radiation have focused mainly on understanding the histopathology. However, to enable medical countermeasure assessment under the animal rule criteria, it is necessary to have a robust model in which the relationship between radiation dose and intestinal radiation syndrome incidence, timing and severity are established and correlated with histopathology. Although many mortality studies have been published, they have used a variety of mouse strains, ages, radiation sources and husbandry conditions, all of which influence the dose response. Further, it is clear that the level of bone marrow irradiation and supportive care can influence endpoints. In order to create robust baseline data we have generated dose response data in adult male mice, maintained under identical conditions, and exposed to either total or partial-body irradiation. Partial-body irradiation includes both extensive (40%) and minimal (5%) bone marrow sparing models, the latter designed to correlate with an established primate model and allow assessment of effects of any medical countermeasure on all three major radiation syndromes (intestinal, bone marrow and lung) in the surviving mice. Lethal dose (LD30, LD50 and LD70) data are described in the various models, along with the impact of enteric flora and response to supportive care. Correlation with diarrhea severity and histopathology are also described. This data can be used to aid the design of good laboratory practice (GLP) compliant Animal Rule studies that are reflective of the conditions following accidental radiation exposure.

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Section: Discussionmentioning

confidence: 99%

Acute Gastrointestinal Syndrome in High-Dose Irradiated Mice

Booth¹,

Tudor²,

Tudor³

et al. 2012

Health Physics

174

185

View full text Add to dashboard Cite

show abstract

“…[43][44][45] Higher doses can cause the animals to die secondary to irradiation-induced toxicity while lower doses may prolong the time necessary to achieve sufficient donor engraftment. 44 Fifty-six 6-month-old C57BL/6 male mice were divided into two groups.…”

Section: Total Body Irradiationmentioning

confidence: 99%

Total Body Irradiation Is Permissive for Mesenchymal Stem Cell-Mediated New Bone Formation Following Local Transplantation

Herberg

Kondrikova

Hussein

et al. 2014

Tissue Engineering Part A

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Skeletal injury is a major clinical challenge accentuated by the decrease of bone marrow-derived mesenchymal stem/stromal cells (BMSCs) with age or disease. Numerous experimental and clinical studies have revealed that BMSCs hold great promise for regenerative therapies due to their direct osteogenic potential and indirect trophic/ paracrine actions. Increasing evidence suggests that stromal cell-derived factor-1 (SDF-1) is involved in modulating the host response to the injury. Common problems with BMSC therapy include poor cell engraftment, which can be addressed by total body irradiation (TBI) prior to transplantation. In this study, we tested the hypothesis that direct tibial transplantation of BMSCs drives endogenous bone formation in a dose-dependent manner, which is enhanced by TBI, and investigated the potential role of SDF-1 in facilitating these events. We found that TBI is permissive for transplanted BMSCs to engraft and contribute to new bone formation. Bone marrow (BM) interstitial fluid analysis revealed no differences of SDF-1 splice variants in irradiated animals compared to controls, despite the increased mRNA and protein levels expressed in whole BM cells. This correlated with increased dipeptidyl peptidase IV activity and the failure to induce chemotaxis of BMSCs in vitro. We found increased mRNA expression levels of the major SDF-1-cleaving proteases in whole BM cells from irradiated animals suggesting distinct spatial differences within the BM in which SDF-1 may play different autocrine and paracrine signaling roles beyond the immediate cell surface microenvironment.

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“…Using only data points from 7.5 or 10 Gy and higher did not significantly decrease the D 0 in our study (data not shown). One possible explanation for the inter-study discrepancies could be variations in inherent radiosensitivity between different mouse strains [18]. Since radiation doses of 14 to 17 Gy lead to a near complete eradication of jejunal crypts, we chose to use only doses up to 10 Gy in the combined chemoradiation experiments.…”

Section: Discussionmentioning

confidence: 99%

The effect on the small bowel of 5-FU and oxaliplatin in combination with radiation using a microcolony survival assay

et al. 2009

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BackgroundIn locally advanced rectal cancer, 5-Fluorouracil (5-FU)-based chemoradiation is the standard treatment. The main acute toxicity of this treatment is enteritis. Due to its potential radiosensitizing properties, oxaliplatin has recently been incorporated in many clinical chemoradiation protocols. The aim of this study was to investigate to what extent 5-FU and oxaliplatin influence the radiation (RT) induced small bowel mucosal damage when given in conjunction with single or split dose RT.MethodsImmune competent balb-c mice were treated with varying doses of 5-FU, oxaliplatin (given intraperitoneally) and total body RT, alone or in different combinations in a series of experiments. The small bowel damage was studied by a microcolony survival assay. The treatment effect was evaluated using the inverse of the slope (D0) of the exponential part of the dose-response curve.ResultsIn two separate experiments the dose-response relations were determined for single doses of RT alone, yielding D0 values of 2.79 Gy (95% CI: 2.65 - 2.95) and 2.98 Gy (2.66 - 3.39), for doses in the intervals of 5-17 Gy and 5-10 Gy, respectively. Equitoxic low doses (IC5) of the two drugs in combination with RT caused a decrease in jejunal crypt count with significantly lower D0: 2.30 Gy (2.10 - 2.56) for RT+5-FU and 2.27 Gy (2.08 - 2.49) for RT+oxaliplatin. Adding both drugs to RT did not further decrease D0: 2.28 Gy (1.97 - 2.71) for RT+5-FU+oxaliplatin. A clearly higher crypt survival was noted for split course radiation (3 × 2.5 Gy) compared to a single fraction of 7.5 Gy. The same difference was seen when 5-FU and/or oxaliplatin were added.ConclusionCombining 5-FU or oxaliplatin with RT lead to an increase in mucosal damage as compared to RT alone in our experimental setting. No additional reduction of jejunal crypt counts was noted when both drugs were combined with single dose RT. The higher crypt survival with split dose radiation indicates a substantial recovery between radiation fractions. This mucosal-sparing effect achieved by fractionation was maintained also when chemotherapy was added.

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Comparison of Intestine and Bone Marrow Radiosensitivity of the BALB/c and the C57BL/6 Mouse Strains and Their B6CF 1 Offspring

Cited by 36 publications

References 8 publications

Acute Gastrointestinal Syndrome in High-Dose Irradiated Mice

Acute Gastrointestinal Syndrome in High-Dose Irradiated Mice

Total Body Irradiation Is Permissive for Mesenchymal Stem Cell-Mediated New Bone Formation Following Local Transplantation

The effect on the small bowel of 5-FU and oxaliplatin in combination with radiation using a microcolony survival assay

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