Amelioration of Mucositis in Proton Therapy of Fanconi Anemia Fanca-/- Mice by JP4-039

In Vivo. 2019 Nov-Dec;33(6):1757-1766. doi: 10.21873/invivo.11666.

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.

Keywords: Fanconi anemia; mucositis; proton; radiation protector; toxicity.

MeSH terms

  • Animals
  • Cell Line
  • Fanconi Anemia / metabolism
  • Fanconi Anemia / radiotherapy*
  • Fanconi Anemia Complementation Group A Protein / metabolism
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Mesenchymal Stem Cells / radiation effects
  • Mice
  • Mucositis / drug therapy*
  • Mucositis / metabolism
  • Nitrogen Oxides / pharmacology*
  • Proton Therapy / adverse effects*
  • Radiation Tolerance / drug effects
  • Radiation-Protective Agents / pharmacology*

Substances

  • Fanconi Anemia Complementation Group A Protein
  • JP4-039
  • Nitrogen Oxides
  • Radiation-Protective Agents