Fanconi Anemia Mouse Genotype-specific Mitigation of Total Body Irradiation by GS-Nitroxide JP4-039.

Background/aim: Radiation mitigator, GS-nitroxide, JP4-039, was evaluated for mitigation of total body irradiation (TBI) in Fanconi anemia (FA) Fancd2 (129/Sv), Fancg (B6), and Fanca (129/Sv) mice.

Materials And Methods: JP4-039 dissolved in 30% 2-hydroxypropyl-β-cyclodextrin was injected intramuscularly 24 h after total body irradiation (9.25 Gy) into Fanca, Fancd2 and Fancg mice. Irradiation survival curves were performed in vitro using bone marrow stromal cell lines derived from Fanca, Fancd2 and Fancg mice.

Results: FA mice demonstrate genotype specific differences in TBI mitigation by JP4-039. Radiation effects in derived bone marrow stromal cell lines in vitro were mitigated by drugs that block apoptosis, but not necroptosis or ferroptosis.

Conclusion: FA mouse models are valuable for elucidating DNA repair pathways in cell and tissue responses to TBI, and the role of drugs that target distinct cell death pathways.