Prophylactically Feeding Manganese to Drosophila Confers Sex-Specific Protection from Acute Ionizing Radiation Independent of MnSOD2 Levels

Ionizing radiation is a health threat to many, including warfighters, radiological emergency responders, radiotherapy patients, and astronauts. Despite this, no FDA-approved prophylactic medical countermeasures exist to attenuate the symptoms that occur from radiation exposure. Manganese has recently been shown to be critical for radioresistance in a wide range of organisms. In this study, we designed a stringent feeding method to test the prophylactic effects of dietary manganese on Drosophila’s lifespan before exposure to acute irradiation. We found that male flies have substantially lower radioresistance than females, but feeding with low doses of MnCl₂ before acute irradiation exposure extends male survival to that of females. Whole animal electron paramagnetic resonance analyses showed males have lower amounts of high-symmetry manganese-metabolite antioxidant complexes (H-Mn) than females, but manganese supplementation increases H-Mn to female levels. Levels of mitochondrial free-radical scavenger manganese-superoxide-dismutase 2 (MnSOD2) did not increase after acute irradiation, nor did loss of MnSOD2 sensitize larvae to acute irradiation exposure. These data support that prophylactic manganese feeding is sufficient to increase survivorship in males subjected to acute irradiation, independent of MnSOD2 levels, indicating a role of antioxidant manganese-metabolite H-Mn complexes for radioprotection. Furthermore, this Drosophila feeding method could be used to identify additional radiation countermeasures.