Mouse Models for Efficacy Testing of Agents against Radiation Carcinogenesis — A Literature Review

Rivina, Leena; Schiestl, Robert H.

doi:10.3390/ijerph10010107

Cited by 8 publications

(3 citation statements)

References 201 publications

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“…Cancers arising from precursor or immature T cells developing within the thymus [ 15 ], presenting as massive clonal expansion of thymic T cells (with or without involvement of peripheral lymphoid organs), are one of the principal tumours induced in mice exposed to whole-body irradiation (reviewed in [ 16 ]). Although the incidence following irradiation varies across inbred mouse strains, T cell lymphomas (TL) generally have short latency (within 3–9 months following irradiation), occur infrequently in control mice, and show characteristic changes in one or more key tumour suppressor genes (TSG) or oncogenes [ 17 – 20 ].…”

Section: Introductionmentioning

confidence: 99%

Genetic Analysis of T Cell Lymphomas in Carbon Ion-Irradiated Mice Reveals Frequent Interstitial Chromosome Deletions: Implications for Second Cancer Induction in Normal Tissues during Carbon Ion Radiotherapy

Blyth¹,

Kakinuma²,

Sunaoshi³

et al. 2015

PLoS ONE

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Monitoring mice exposed to carbon ion radiotherapy provides an indirect method to evaluate the potential for second cancer induction in normal tissues outside the radiotherapy target volume, since such estimates are not yet possible from historical patient data. Here, male and female B6C3F1 mice were given single or fractionated whole-body exposure(s) to a monoenergetic carbon ion radiotherapy beam at the Heavy Ion Medical Accelerator in Chiba, Japan, matching the radiation quality delivered to the normal tissue ahead of the tumour volume (average linear energy transfer = 13 keV.μm-1) during patient radiotherapy protocols. The mice were monitored for the remainder of their lifespan, and a large number of T cell lymphomas that arose in these mice were analysed alongside those arising following an equivalent dose of 137Cs gamma ray-irradiation. Using genome-wide DNA copy number analysis to identify genomic loci involved in radiation-induced lymphomagenesis and subsequent detailed analysis of Notch1, Ikzf1, Pten, Trp53 and Bcl11b genes, we compared the genetic profile of the carbon ion- and gamma ray-induced tumours. The canonical set of genes previously associated with radiation-induced T cell lymphoma was identified in both radiation groups. While the pattern of disruption of the various pathways was somewhat different between the radiation types, most notably Pten mutation frequency and loss of heterozygosity flanking Bcl11b, the most striking finding was the observation of large interstitial deletions at various sites across the genome in carbon ion-induced tumours, which were only seen infrequently in the gamma ray-induced tumours analysed. If such large interstitial chromosomal deletions are a characteristic lesion of carbon ion irradiation, even when using the low linear energy transfer radiation to which normal tissues are exposed in radiotherapy patients, understanding the dose-response and tissue specificity of such DNA damage could prove key to assessing second cancer risk in carbon ion radiotherapy patients.

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Section: Introductionmentioning

confidence: 99%

Genetic Analysis of T Cell Lymphomas in Carbon Ion-Irradiated Mice Reveals Frequent Interstitial Chromosome Deletions: Implications for Second Cancer Induction in Normal Tissues during Carbon Ion Radiotherapy

Blyth¹,

Kakinuma²,

Sunaoshi³

et al. 2015

PLoS ONE

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“…One study reported that a lethal dose of radiation for 70% mice within 30 days (level of LD70/30) by total-body irradiation was 10.5–12 Gy [ 30 ]. Induction of leukemia in mice with ionizing radiation was reported at doses of 3–4.25 Gy [ 31 ]. Wernle et al reported that 5 Gy units of local irradiation to mice hind limb could significantly change the bone morphology and strength with time [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Development of an experimental model for radiation-induced inhibition of cranial bone regeneration

Jung

Lee

et al. 2018

Maxillofac Plast Reconstr Surg

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BackgroundRadiation therapy is widely employed in the treatment of head and neck cancer. Adverse effects of therapeutic irradiation include delayed bone healing after dental extraction or impaired bone regeneration at the irradiated bony defect. Development of a reliable experimental model may be beneficial to study tissue regeneration in the irradiated field. The current study aimed to develop a relevant animal model of post-radiation cranial bone defect.MethodsA lead shielding block was designed for selective external irradiation of the mouse calvaria. Critical-size calvarial defect was created 2 weeks after the irradiation. The defect was filled with a collagen scaffold, with or without incorporation of bone morphogenetic protein 2 (BMP-2) (1 μg/ml). The non-irradiated mice treated with or without BMP-2-included scaffold served as control. Four weeks after the surgery, the specimens were harvested and the degree of bone formation was evaluated by histological and radiographical examinations.ResultsBMP-2-treated scaffold yielded significant bone regeneration in the mice calvarial defects. However, a single fraction of external irradiation was observed to eliminate the bone regeneration capacity of the BMP-2-incorporated scaffold without influencing the survival of the animals.ConclusionThe current study established an efficient model for post-radiation cranial bone regeneration and can be applied for evaluating the robust bone formation system using various chemokines or agents in unfavorable, demanding radiation-related bone defect models.

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“…Numerous ex vivo human cell line radiation studies have explored cytogenic markers, nucleotide pool damage, and mutations [ 7 ] and showed significant changes in gene expression in response to radiation under heterogeneous experimental conditions [ 8 , 9 ]. Likewise, the limited radiation studies in animal models have been heterogeneous and demonstrated distinct changes in gene expression in various tissues [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Transcriptomes of Wet Skin Biopsies Predict Outcomes after Ionizing Radiation Exposure with Potential Dosimetric Applications in a Mouse Model

Alkhalil

Clifford

Miller

et al. 2022

CIMB

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Countermeasures for radiation diagnosis, prognosis, and treatment are trailing behind the proliferation of nuclear energy and weaponry. Radiation injury mechanisms at the systems biology level are not fully understood. Here, mice skin biopsies at h2, d4, d7, d21, and d28 after exposure to 1, 3, 6, or 20 Gy whole-body ionizing radiation were evaluated for the potential application of transcriptional alterations in radiation diagnosis and prognosis. Exposure to 20 Gy was lethal by d7, while mice who received 1, 3, or 6 Gy survived the 28-day time course. A Sammon plot separated samples based on survival and time points (TPs) within lethal (20 Gy) and sublethal doses. The differences in the numbers, regulation mode, and fold change of significantly differentially transcribed genes (SDTGs, p < 0.05 and FC > 2) were identified between lethal and sublethal doses, and down and upregulation dominated transcriptomes during the first post-exposure week, respectively. The numbers of SDTGs and the percentages of upregulated ones revealed stationary downregulation post-lethal dose in contrast to responses to sublethal doses which were dynamic and largely upregulated. Longitudinal up/downregulated SDTGs ratios suggested delayed and extended responses with increasing IR doses in the sublethal range and lethal-like responses in late TPs. This was supported by the distributions of common and unique genes across TPs within each dose. Several genes with potential dosimetric marker applications were identified. Immune, fibrosis, detoxification, hematological, neurological, gastric, cell survival, migration, and proliferation radiation response pathways were identified, with the majority predicted to be activated after sublethal and inactivated after lethal exposures, particularly during the first post-exposure week.

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Mouse Models for Efficacy Testing of Agents against Radiation Carcinogenesis — A Literature Review

Cited by 8 publications

References 201 publications

Genetic Analysis of T Cell Lymphomas in Carbon Ion-Irradiated Mice Reveals Frequent Interstitial Chromosome Deletions: Implications for Second Cancer Induction in Normal Tissues during Carbon Ion Radiotherapy

Genetic Analysis of T Cell Lymphomas in Carbon Ion-Irradiated Mice Reveals Frequent Interstitial Chromosome Deletions: Implications for Second Cancer Induction in Normal Tissues during Carbon Ion Radiotherapy

Development of an experimental model for radiation-induced inhibition of cranial bone regeneration

Transcriptomes of Wet Skin Biopsies Predict Outcomes after Ionizing Radiation Exposure with Potential Dosimetric Applications in a Mouse Model

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