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.

FIG. 1

Survival of mice exposed to proton and iron-ion radiation. Male ICR mice aged 4–5 weeks were irradiated with 3 Gy of 1 GeV/nucleon protons or 1 GeV/nucleon iron ions at the Brookhaven National Laboratory. The animals were maintained on the AIN-93G rodent diet (Control Diet) and observed for 2 years after the radiation exposure. P < 0.05 for 1 GeV/nucleon iron ions compared to sham exposure; P < for protons compared to sham exposure.

FIG. 2

Survival of mice exposed to proton radiation. Male ICR mice aged 4–5 weeks were irradiated with 3 Gy of 1 GeV protons at the Brookhaven National Laboratory. The animals were maintained on the AIN-93G rodent diet with or without (Control) supplementation of anti-oxidants or BBIC and observed for 2 years after the radiation exposure. P > 0.5 for antioxidants compared to control diet; P > 0.2 for BBIC compared to control diet.

FIG. 3

Survival of mice exposed to 1 GeV/nucleon iron-ion radiation. Male ICR mice aged 4–5 weeks were irradiated with 0.5 Gy of 1 GeV/nucleon iron ions at the Brookhaven National Laboratory. The animals were maintained on the AIN-93G rodent diet with or without (Control) supplementation of antioxidants or BBIC and observed for 2 years after the radiation exposure. P > 0.7 for antioxidants compared to control diet; P > 0.7 for BBIC compared to control diet.

FIG. 4

Effects of antioxidant (AOX) and BBIC supplements on proton- and iron-ion radiation-induced malignant lymphomas or rare tumors. The mice were maintained on diets with or without antioxidant or BBIC supplementation and exposed to 1 GeV/nucleon iron ions (0.5 Gy) or protons (3 Gy). Sham-irradiated animals were included as controls. After the radiation exposure, the animals were returned to their cages and fed the control diet or diets supplemented with antioxidants or BBIC according to the study design and observed for approximately 2 years. The effective number of animals in each treatment group was used to calculate the fractions of animals with malignant lymphoma or rare tumors. The fractions of mice with malignant lymphomas (panel A) and/or rare tumors (panel B) were compared by Fisher’s exact test (panel A) or a χ² test (panel B). Due to the low incidence rates of lymphoma and rare tumors in individual treatment groups, the nine treatment groups (described in Tables 2 and 3) were merged into the following treatment groups for statistical analysis by a χ² test (panel B): Sham Radiation (Groups 1, 2 and 3), Radiation (Groups 4 and 7), and Radiation plus BBIC or Anti-oxidant (Goups 5, 6, 8 and 9).