ArticleRadiation research2014
Amelioration of radiation-induced oral cavity mucositis and distant bone marrow suppression in fanconi anemia Fancd2-/- (FVB/N) mice by intraoral GS-nitroxide JP4-039.
Article in Radiation research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 37 citations in OpenAlex.
- Targeting Mitochondrial Reactive Oxygen Species: JP4-039's Potential as a Cardiovascular Therapeutic.Journal of clinical medicine · 2025Review
- Fanconi anemia patients with head and neck squamous cell carcinoma - a multi-center study.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2025Article
- Nitroxides: Chemistry, Antioxidant Properties, and Biomedical Applications.Molecules (Basel, Switzerland) · 2025Review
- JP4-039 Mitigates Cisplatin-Induced Acute Kidney Injury by Inhibiting Oxidative Stress and Blocking Apoptosis and Ferroptosis in Mice.Antioxidants (Basel, Switzerland) · 2024Article
- TGFβ pathway is required for viable gestation of Fanconi anemia embryos.PLoS genetics · 2022Article
- Review
- Intestinal Radiation Protection and Mitigation by Second-Generation ProbioticInternational journal of molecular sciences · 2022Article
- Gene Therapy for Systemic or Organ Specific Delivery of Manganese Superoxide Dismutase.Antioxidants (Basel, Switzerland) · 2021Review
- Anti-Ferroptosis Drug Enhances Total-Body Irradiation Mitigation by Drugs that Block Apoptosis and Necroptosis.Radiation research · 2020Article
- Mitochondrial energetics is impaired in very long-chain acyl-CoA dehydrogenase deficiency and can be rescued by treatment with mitochondria-targeted electron scavengers.Human molecular genetics · 2019Article
- Intercellular communications-redox interactions in radiation toxicity; potential targets for radiation mitigation.Journal of cell communication and signaling · 2019Review
- Amelioration of Head and Neck Radiation-Induced Mucositis and Distant Marrow Suppression in FancaRadiation research · 2018Article
- Evaluation of mitochondrial bioenergetics, dynamics, endoplasmic reticulum-mitochondria crosstalk, and reactive oxygen species in fibroblasts from patients with complex I deficiency.Scientific reports · 2018Article
- Improved Total-Body Irradiation Survival by Delivery of Two Radiation Mitigators that Target Distinct Cell Death Pathways.Radiation research · 2018Article
- Mitochondria-Targeted Triphenylphosphonium-Based Compounds: Syntheses, Mechanisms of Action, and Therapeutic and Diagnostic Applications.Chemical reviews · 2017Review
- Effectiveness of Analogs of the GS-Nitroxide, JP4-039, as Total Body Irradiation Mitigators.In vivo (Athens, Greece) · 2017Article
- FANCD2 protects against bone marrow injury from ferroptosis.Biochemical and biophysical research communications · 2016Article
- Evolution of malignant plasmacytoma cell lines from K14E7 Fancd2-/- mouse long-term bone marrow cultures.Oncotarget · 2016Article
- Intraoral Mitochondrial-Targeted GS-Nitroxide, JP4-039, Radioprotects Normal Tissue in Tumor-Bearing Radiosensitive Fancd2(-/-) (C57BL/6) Mice.Radiation research · 2016Article
- Antioxidant Approaches to Management of Ionizing Irradiation Injury.Antioxidants (Basel, Switzerland) · 2015Article
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
The altered DNA damage response pathway in patients with Fanconi anemia (FA) may increase the toxicity of clinical radiotherapy. We quantitated oral cavity mucositis in irradiated Fanconi anemia Fancd2(-/-) mice, comparing this to Fancd2(+/-) and Fancd2(+/+) mice, and we measured distant bone marrow suppression and quantitated the effect of the intraoral radioprotector GS-nitroxide, JP4-039 in F15 emulsion. We found that FA mice were more susceptible to radiation injury and that protection from radiation injury by JP4-039/F15 was observed at all radiation doses. Adult 10-12-week-old mice, of FVB/N background Fancd2(-/-), Fancd2(+/-) and Fancd2(+/+) were head and neck irradiated with 24, 26, 28 or 30 Gy (large fraction sizes typical of stereotactic radiosurgery treatments) and subgroups received intraoral JP4-039 (0.4 mg/mouse in 100 μL F15 liposome emulsion) preirradiation. On day 2 or 5 postirradiation, mice were sacrificed, tongue tissue and femur marrow were excised for quantitation of radiation-induced stress response, inflammatory and antioxidant gene transcripts, histopathology and assay for femur marrow colony-forming hematopoietic progenitor cells. Fancd2(-/-) mice had a significantly higher percentage of oral mucosal ulceration at day 5 after 26 Gy irradiation (59.4 ± 8.2%) compared to control Fancd2(+/+) mice (21.7 ± 2.9%, P = 0.0063). After 24 Gy irradiation, Fancd2(-/-) mice had a higher oral cavity percentage of tongue ulceration compared to Fancd2(+/+) mice irradiated with higher doses of 26 Gy (P = 0.0123). Baseline and postirradiation oral cavity gene transcripts were altered in Fancd2(-/-) mice compared to Fancd2(+/+) controls. Fancd2(-/-) mice had decreased baseline femur marrow CFU-GM, BFUe and CFU-GEMM, which further decreased after 24 or 26 Gy head and neck irradiation. These changes were not seen in head- and neck-irradiated Fancd2(+/+) mice. In radiosensitive Fancd2(-/-) mice, biomarkers of both local oral cavity and distant marrow radiation toxicity were ameliorated by intraoral JP4-039/F15. We propose that Fancd2(-/-) mice are a valuable radiosensitive animal model system, which can be used to evaluate potential radioprotective agents.
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