Exposure to radiation can cause oxidative stress in cells. Oxidative stress is an increase in the levels of highly reactive oxygen derivatives that cause damage to critical molecules in our cells such as membrane proteins and DNA. Dr. Ann Kennedy is determining whether oxidative stress levels are related to cancer occurrence and whether oxidative stress levels can be used to predict cancer risk. In addition, she is evaluating which types of dietary supplements will reduce oxidative stress levels and cancer risk.
Overview
Countermeasures for Space Radiation Biological Effects
Principal Investigator:
Ann R. Kennedy, D.Sc.
Organization:
University of Pennsylvania School of Medicine
Technical Summary
It is our hypothesis that control of radiation-induced oxidative stress will reduce the risk of cancer development. In this work, there are two major specific aims: to determine whether certain dietary supplements can reduce space radiation-induced oxidative stress in cultured human cells, and to determine whether the dietary supplements shown to reduce oxidative stress in cultured cells have effects on space radiation-induced oxidative stress in animal model systems. The supplemental agents evaluated alone and in combinations include vitamins C, E, folic acid, glutathione, N-acetyl cysteine (NAC), selenomethionine (SeM), alpha-lipoic acid, niacin, thiamin, Co-enzyme Q10 and the soybean-derived Bowman-Birk inhibitor.
The levels of oxidative stress in cultured cells are determined by a dichlorofluorescein fluorescence assay, which has been adapted for the evaluation of effects from space radiation as part of this project. In animals, the total antioxidant status (TAS) in serum or plasma samples is used as the indicator of oxidative stress. The agents shown to reduce space radiation-induced oxidative stress in vitro (in MCF10 cells, a human breast epithelial cell line) include vitamin C, vitamin E succinate, NAC, SeM, alpha-lipoic acid (in the reduced form) and Co-enzyme Q10. The effects of treatment with this combination of dietary supplement agents on bio-reduction capacity in animals were evaluated in rats irradiated with iron ions, protons or gamma-rays at a dose of 200 cGy.
Sham-irradiated animals were used as controls. The results demonstrated that the TAS decreased in the irradiated animals fed with the control diet. The control animal diet (AIN-93G) contained many of the nutritional supplements at levels comparable on a weight basis to the human RDA levels. Supplementation of the diet with the nutritional supplements prevented the drop in the serum or plasma TAS after the radiation exposure. These results suggest that diet supplementation was effective in preventing the reduction in TAS in the animals irradiated with all three types of radiation. These results indicated that both serum and plasma samples are suitable for a determination of TAS in the irradiated animals.
Our results indicate that the dietary supplement agents evaluated can reduce the levels of radiation-induced oxidative stress in both in vitro and in vivo systems.
Earth Applications
There are many individuals on Earth who are exposed to higher-than-normal background radiation levels. These would include individuals who are occupationally exposed to radiation such as workers in the nuclear power industry, those employed in universities and hospitals who work with radiation, those treated with radiation as part of medical procedures, airline flight crews and those who frequently travel by air, etc. The countermeasures developed as part of this NSBRI-funded research could greatly benefit these individuals as well as those involved in space travel.
This project's funding ended in 2004