Recent evidence has supported a prominent role for antioxidants in ameliorating the chronic effects of radiation exposure. These experimental models have demonstrated the importance of antioxidant therapy in ameliorating the acute effects of radiation. Administration of antioxidant agents including manganese superoxide dismutase plasmid liposome gene product and small molecule antioxidants ( 4, 5) has been shown to decrease radiation-induced cellular apoptosis, tissue injury and improved survival in organ-specific- and total-body-irradiated rodents ( 6– 7 8 9 10 11 12). Depletion of antioxidants at the mitochondria is associated with disruption of cytochrome C binding to cardiolipin, mitochondrial membrane disruption, and leakage into the cytoplasm of cytochrome C, which then initiates a cascade of molecular events leading to apoptosis ( 3). The molecular events that occur early in the initiation of apoptosis originate at the mitochondrial membrane and include molecular sequelae of both oxidative and nitrosative stress, producing rapid depletion of antioxidant stores ( 2). Ionizing radiation induces nuclear DNA strand breaks that initiate a transfer to the mitochondria of both pro-apoptotic and anti-apoptotic molecules ( 1). Survivors of acute ionizing radiation damage have ameliorated life shortening if they are fed an antioxidant-chemopreventive diet. In addition, mice treated with MnSOD-PL only and surviving 30 days after radiation also had increased survival compared to those on the regular diet alone ( P = 0.02). The mice on the antioxidant-chemoprevention diet alone or with MnSOD-PL that survived 30 days after irradiation had a significant increase in survival compared to mice on the regular diet ( P = 0.04 or 0.01, respectively).
KEY TO HIGHER ALGEBRA BY HALL AND KNIGHT PLUS
Mice on either diet treated with MnSOD-PL showed decreased death after irradiation compared to irradiated mice on the house diet alone ( P = 0.031 for the house diet plus MnSOD-PL or 0.015 for antioxidant diet plus MnSOD-PL).
Twenty-four hours before the LD 50/30 dose of 9.5 Gy TBI, subgroups of mice were injected intravenously with MnSOD-PL (100 μg plasmid DNA in 100 μl of liposomes). We evaluated the effect of an antioxidant-chemopreventive diet compared to a regular diet on long-term survival in female mice.
C57BL/6NHsd mice receiving intravenous MnSOD-PL prior to 9.5 Gy total-body irradiation (TBI) show increased survival from the acute hematopoietic syndrome, and males demonstrated improved long-term survival (Epperly et al., Radiat.
Many acute and chronic effects of ionizing radiation are mediated by reactive oxygen species and reactive nitrogen species, which deplete antioxidant stores, leading to cellular apoptosis, stem cell depletion and accelerated aging.