Preventing DNA injury from ionizing radiation with oral antioxidants
Antioxidants ingested before exposure to radiation from imaging protects cells from DNA damage, according to findings from a proof-of-principle study published in the Journal of Vascular and Interventional Radiology. Ongoing research at Toronto Western Hospital in Ontario suggests that antioxidants may provide an effective, inexpensive means to protect patients, and may reduce occupational risk to radiologists, technologists, and other health care professionals.
Clinicians and support staff who experience daily radiation exposure are at risk of developing cataracts, radiation fibrosis, and left-sided brain tumors. Published studies suggest that for every 10 mSv of low-dose ionizing radiation, there is an estimated 3% increase in age- and sex-adjusted cancer over a 5-year period.
A cancer begins with the mutation of a gene or multiple genes within a cell. Acquired mutations are caused from damage to DNA in somatic cells. DNA-repair genes fix mistakes of cellular mutation and repair replication errors. If these mutate, subsequent accumulations of cancer-causing mutations may occur. Ionizing radiation can affect the DNA repair process causing molecular changes in the DNA. These changes include single-strand and double-strand breaks, cross-links and sugar/ribose alterations.
Principal investigator Kieran Murphy, MD, an interventional neuroradiologist, and colleagues in the Department of Medical Imaging, initiated this study to evaluate the efficacy of oral antioxidant treatment given to patients before imaging procedures in reducing X-ray-induced damage. Their research was based on the fact that antioxidants exert their effect by scavenging hazardous free radicals that are created by the interaction between ionizing radiation and water molecules before the free radicals can interact with and damage DNA.
The authors recruited 10 consecutive patients undergoing technetium-99m methylene diphosophonate (99mTc MDP) bone scans. None of these patients had had any ionizing imaging procedures in the past seven days or chemotherapy/radiotherapy within the prior six months. The average activity of the dose injected was 798 mβq, with a range of 757-829 mβq.
The first five patients were enrolled in the control group, and the second in the antioxidant group. The oral antioxidant medication consisted of 2 g ascorbate, 1.2 g N-acetylcysteine, 600 mg lipoic acid, and 30 mg beta carotine administered 15 minutes before radiotracer injection. Blood samples for all patients were taken before the injection of the radiotracer and 2.5 hours later. The quantity of the DNA damage of each of the two blood samples was assessed to identify any significant differences.
The authors visualized DNA damage in peripheral blood mononuclear cells (PBMCs) before and after bone scans using 3D microscopy and fluorescently labeled gamma-H2AX protein. Levels of baseline DNA damage were similar to control patients. They reported a significantly higher number of gamma-H2AX foci/cell after ionization radiation in the control group compared with the antioxidant group. Foci in PBMCs from the five patients in the antioxidant group did not increase 2.5 hours after radiotracer injection.
“By studying patients undergoing 99mTc MDP bone scans, a very controlled and long half-life radiation exposure, similar to a prolonged interventional procedure, could be evaluated. All patients received a known dose of tracer. There were no known confounding variables that could have affected results … . Therefore, the only cause of DNA damage was exposure to the 99mTc MDP tracer,” they stated.
The authors suggest that the use of antioxidants could prevent long-term sustained DNA damage in patients who undergo repeated screening imaging studies with ionizing radiation. They also believe that this might be a protection strategy for interventional radiologists.
Dr. Murphy said further research is being planned. These include clinical trials with a larger number of cohorts in Canada and one in the United States. He and his colleagues are studying different kinds of antioxidant formulations and the timing for administration. Dr. Murphy stated that additional research will be needed to match the pharmacokinetics and bioavailability of any chosen antioxidant mixture with the effective half-life and biodistribution of specific radiopharmaceuticals.
The research team also plans to perform randomized prospective studies of interventional radiologists and their staff. They said that angiography technologists and interventionalists represent an excellent long-term study group to follow to evaluate the potential oncologic protective benefit of antioxidants.
REFERENCES
- Murphy KJ, Velauthapillai N, Barfett J, et al. Antioxidants taken orally 1 hour prior to radiation exposure can prevent DNA injury. J Vas Interv Radiol. 2015. 26;2: S114.
- Murphy K, Thakore A, Lacasse MC, et al. Should future interventional neuroradiologists e screened for mutations that imapir radiation-induced DNA repair? Interven Neuroradiol. 2017 23;1: 5-7.
- Velauthapillai N, Barfett J, Jaffer H, et al. Antioxidants Taken Orally prior to Diagnostic Radiation Exposure Can Prevent DNA Injury. J Vas Interv Radiol. Published online December 26, 2016.