Abstract 1660: JP4-039/F14 treatment of E13 pregnant mice 24 hours after total body irradiation (TBI) improves survival, growth and development of fetal mice

Purpose: A practical radiation mitigator must be safe in pregnant females. Irradiation during pregnancy can induce fetal death, stunt growth, and/or lead to teratogenic and carcinogenic effects dependent on stage of gestation. We evaluated the mitochondrial targeted GS-nitroxide mitigator JP4-039 for effects on total body irradiated(TBI) pregnant mice. Methods: Timed pregnant C57Bl/6NHsd mice at E13 were irradiated to 3 Gy, subgroups were injected IV 24 hr later (E14) with JP4-039 in F14 emulsion (4 ug JP4-039 in 100 ul of F14). Mice were followed for number of pups born, weight of pups at day 5 after birth, and for number of survivors at time of weaning. In other studies of irradiation effects, new- born pups, on the day of delivery, were euthanized, fixed, sectioned and examined microscopically. Results: Nonirradiated mice showed 97 ± 2% of newborn surviving until weaning. Pups born to 3 Gy irradiated E13 pregnant mice had decreased survival (8.3 ± 8.7%) (p Conclusions: Treatment of total body irradiatedE13 pregnant mice at E14 with JP4-039/F14 was safe and effective as a radiation mitigator, led to increased numbers of surviving newborns, improved growth and development, and after weaning over 21 days, and increased body weight with no late deaths. Supported by NIAID/NIH U19-AI068021 Citation Format: Michael W. Epperly, Lora Rigatti, Tracy Dixon, Song Li, Joel S. Greenberger. JP4-039/F14 treatment of E13 pregnant mice 24 hours after total body irradiation(TBI) improves survival, growth and development of fetal mice. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1660.