Effects of Dietary Antioxidant Supplementation on the Development of Malignant Lymphoma and Other Neoplastic Lesions in Mice Exposed to Proton or Iron-Ion Radiation

Abstract

Malignancy is considered to be a particular risk associated with exposure to the types of ionizing radiation encountered during extended space flight. In the present study, two dietary preparations were evaluated for their ability to prevent carcinogenesis in CBA mice exposed to different forms of space radiation: protons and highly energetic heavy particles (HZE particles). One preparation contained a mixture of antioxidant agents. The other contained the soybean-derived Bowman-Birk protease inhibitor (BBI), used in the form of BBI Concentrate (BBIC). The major finding was that there was a reduced risk of developing malignant lymphoma in animals exposed to space radiation and maintained on diets containing the antioxidant formulation or BBIC compared to the irradiated animals maintained on the control diet. In addition, the two different dietary countermeasures also reduced the yields of a variety of different rare tumor types observed in the animals exposed to space radiation. These results suggest that dietary supplements could be useful in the prevention of malignancies and other neoplastic lesions developing from exposure to space radiation.

Dietary Supplements Reduce the Cataractogenic Potential of Proton and HZE-Particle Radiation in Mice

“…As reported previously, there were no statistically significant differences in the survival of the irradiated animals (protons or iron ions) on the antioxidant or BBIC diets compared to the survival of irradiated animals maintained on the control diet (18). Therefore, there would not have been a bias in the cataract analyses resulting from the date the animals were killed.…”

“…The animals evaluated in this study were the same animals evaluated for other end points in a previously reported carcinogenesis study. The survival curves and other data concerning these animals are described in this earlier report (18).…”

“…The cataractogenesis studies presented here used mice exposed to proton and iron-ion radiation as part of long-term studies in which the effects of BBIC and the antioxidant formulation on carcinogenesis were also being assessed; the carcinogenesis data were published previously (18). Pilot studies indicated that the antioxidant or control diets did not affect the weight gain of the experimental animals.…”

“…This formulation of antioxidant agents was developed for its ability to reduce radiationinduced oxidative stress in vitro (14) and radiationinduced oxidative stress in mice and rats exposed to radiation from HZE particles, protons and c rays (12,13,15). In addition, it has the ability to reduce other adverse biological effects associated with radiation exposure, including HZE particle-and proton-induced cytotoxicity and malignant transformation in cultured human thyroid epithelial cells (16), the acute effects of radiation exposure in vivo, which includes effects on hematopoietic cells and animal mortality (17) and carcinogenesis in animals exposed to protons or iron ions (18).…”

The effects of antioxidants on gene expression following gamma-radiation (GR) and proton radiation (PR) in mice in vivo

“…13 These data suggest that the AOX diet had the potential to block cell death through the mitochondrial deathinducing pathway. Interestingly, the same mixture of dietary antioxidants also prevented neoplastic transformation and the development of malignancies in mice following PR, 14 suggesting that dietary antioxidant supplementation could prevent both short-and long-term side-effects that are of concern following radiation treatment.…”