1. Amelioration of Mucositis in Proton Therapy of Fanconi Anemia Fanca−/− Mice by JP4-039
- Author
-
Craig W. Stevens, Peyman Kabolizadeh, Darcy Franicola, Peter Wipf, Stephanie Thermozier, Michael W. Epperly, George S. Wilson, Xuanfeng Ding, Andrew Henderson, Katie Buelow, Joel S. Greenberger, Xiaoqiang Li, Thomas J. Quinn, and Aranee Sivananthan
- Subjects
Mucositis ,Senescence ,congenital, hereditary, and neonatal diseases and abnormalities ,Cancer Research ,Stromal cell ,Radiation-Protective Agents ,Radiation Tolerance ,General Biochemistry, Genetics and Molecular Biology ,Cell Line ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Fanconi anemia ,hemic and lymphatic diseases ,Proton Therapy ,medicine ,Animals ,Pharmacology ,Fanconi Anemia Complementation Group A Protein ,Chemistry ,nutritional and metabolic diseases ,Mesenchymal Stem Cells ,medicine.disease ,FANCA ,Haematopoiesis ,Fanconi Anemia ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Toxicity ,Cancer research ,Nitrogen Oxides ,Bone marrow ,Research Article - Abstract
Background/Aim: We tested JP4-039, a GS-nitroxide radiation damage mitigator in proton therapy of Fanconi anemia (FA) mice. Materials and Methods: Fanca(–/–) and Fanca(+/+) bone marrow stromal cells were pre-treated with JP4-039 and irradiated with either protons or photons (0-10 GyRBE) followed by clonogenic survival and β-Galactosidase senescence analysis. Fanca(–/–) and Fanca(+/+) mice were pretreated with JP4-039 for 10 min prior to oropharyngeal irradiation with either protons or photons (0 or 30 GyRBE) followed by sacrifice and measurement of oral cavity ulceration, distant hematopoietic suppression, and real-time polymerase chain reaction analysis. Results: JP4-039 reduced oral cavity ulceration in Fanca(–/–) mice, transcripts Nfkb, Ap1, Sp1, and Nrf2, and proton therapy induced distant marrow suppression. Conclusion: JP4-039 protected Fanca(–/–) and Fanca(+/+) cells and mouse oral cavity from both proton and photon radiation.
- Published
- 2019