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- Title
Fanconi Anemia Mouse Genotype-specific Mitigation of Total Body Irradiation by GS-Nitroxide JP4-039.
- Authors
EPPERLY, MICHAEL W.; FISHER, RENEE; XICHEN ZHANG; WEN HOU; SHIELDS, DONNA; WIPF, PETER; HONG WANG; THERMOZIER, STEPHANIE; GREENBERGER, JOEL S.
- 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.
- Subjects
FANCONI'S anemia; GENOTYPES; TOTAL body irradiation; CELL death; STROMAL cells
- Publication
In Vivo, 2020, Vol 34, Issue 1, p33
- ISSN
0258-851X
- Publication type
Article
- DOI
10.21873/invivo.11742