Amelioration of mucositis in proton therapy of fanconi anemia fanca-/- Mice by JP4-039

Thomas J. Quinn
Xuanfeng Ding
Xiaoqiang Li
George D. Wilson
Katie Buelow
Aranee Sivananthan, UPMC Hillman Cancer Center
Stephanie Thermozier, UPMC Hillman Cancer Center
Andrew Henderson, UPMC Hillman Cancer Center
Michael W. Epperly, UPMC Hillman Cancer Center
Darcy Franicola, UPMC Hillman Cancer Center
Peter Wipf, University of Pittsburgh
Joel S. Greenberger, UPMC Hillman Cancer Center
Craig W. Stevens
Peyman Kabolizadeh


© 2019 International Institute of Anticancer Research. All rights reserved. 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.