Abstract
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.