The situation at the Fukushima nuclear plant in Japan is giving great urgency to the issue of personal protection against ionizing radiation. This blog entry is about how a degree of personal protection against radiation damage can be achieved by taking antioxidants. I do not think it is an exaggeration to say that what I will be discussing could in the long term save the lives of millions of people.
The Fukushima nuclear disaster
As of this writing the situation at the Fukushima Daiichi reactors remains uncontrolled. It is a slowly-unfolding disaster, appearing to get worse and worse. Smoke or metallic vapor from overheated or melted fuel rods contain large quantities of radioactive fission byproducts. And very little can be done to stop fuel rod overheating without pumping in large quantities of water which releases radioactive pollution into the environment via steam and water runoff. An immense amount of radioactive material has already been released into the atmosphere affecting a vast area of Japan as well as the ocean. Many workers at the plant are expected to die quickly due to radiation exposure. We don’t know how and when the continuing release of radiation can be contained. Much of Japan including Tokyo could be contaminated semi-permanently by fallout resulting in radiation levels orders of magnitude higher than are normally acceptable. Tens of millions of people are likely to be effected.
An excellent source of information on the situation in Japan is the blog All Things Nuclear. The March 30 entry relates: “Today the IAEA has finally confirmed what some analysts have suspected for days: that the concentration per area of long-lived cesium-137 (Cs-137) is extremely high as far as tens of kilometers from the release site at Fukushima Dai-Ichi, and in fact would trigger compulsory evacuation under IAEA guidelines. — The IAEA is reporting that measured soil concentrations of Cs-137 as far away as Iitate Village, 40 kilometers northwest of Fukushima-Dai-Ichi, correspond to deposition levels of up to 3.7 megabecquerels per square meter (MBq/sq. m). This is far higher than previous IAEA reports of values of Cs-137 deposition, and comparable to the total beta-gamma measurements reported previously by IAEA and mentioned on this blog. — This should be compared with the deposition level that triggered compulsory relocation in the aftermath of the Chernobyl accident: the level set in 1990 by the Soviet Union was 1.48 MBq/sq. m. – Thus, it is now abundantly clear that Japanese authorities were negligent in restricting the emergency evacuation zone to only 20 kilometers from the release site.” Other blog entries refer to the release of substantial quantities of radioactive iodine-131 and to how plutonium is being found in soil samples.
Background on nuclear radiation
For the general Japanese public, the biggest concern is not direct radiation from the Fukushima plant but rather radioactive substances which are released into the environment either via the atmosphere or via runoff into the ocean. Radioactive substances can enter the body via the air, groundwater, tap water or foods or vegetables consumed. Three radioactive substances of primary concern are:
Radio iodine-131: Although having a half life of only 8 days, iodine-131 can be dangerous if ingested by someone with a thyroid iodine deficiency. It is a beta radiation emitter, which means the radiation is not a threat unless the emitting substance is inside the body. “Due to its mode of beta decay, iodine-131 is notable for causing mutation and death in cells which it penetrates, and other cells up to several millimeters away. For this reason, high doses of the isotope are sometimes paradoxically less dangerous than low doses, since they tend to kill thyroid tissues which would otherwise become cancerous as a result of the radiation. For example, children treated with moderate dose of I-131 for thyroid adenomas had a detectable increase in thyroid cancer, but children treated with a much higher dose did not(ref).” As long as the damaged Fukushima plant continues to release iodine-131 into the environment, it will be a threat.
Caesium-137: Has a half life of about 30 years and emits beta and gamma radiation. Because it is chemically similar to potassium, it is readily absorbed in vegetables and human bodies. “Caesium-137 is water-soluble, and the biological behavior of caesium is similar to that of potassium and rubidium. After entering the body, caesium gets more or less uniformly distributed throughout the body, with higher concentration in muscle tissues and lower in bones. The biological half-life of caesium is rather short at about 70 days. Experiments with dogs showed that a single dose of 3800 Î¼Ci/kg (approx. 44 Î¼g/kg of caesium-137) is lethal within three weeks(ref).”
Plutonium: Plutonium is a byproduct of nuclear reactions, is the heaviest stable element and has been called ‘the most toxic substance known to man,” emitting alpha, beta and gamma radiation. The most important isotope of plutonium is plutonium-239, with a half-life of 24,100 years.. Plutonium-238 has a half-life of 88 years and emits alpha particles. plutonium-244 has a half-life of about 80 million years. “Isotopes and compounds of plutonium are radioactive poisons that accumulate in bone marrow. Contamination by plutonium oxide (spontaneously oxidized plutonium) has resulted from a number of nuclear disasters and radioactive incidents including military nuclear accidents where nuclear weapons have burned. Studies of the effects of these smaller releases, as well as of the widespread radiation poisoning sickness and death following the Atomic bombings of Hiroshima and Nagasaki, have provided considerable information regarding the dangers, symptoms and prognosis of radioactive poisoning. PMID 19454804(ref).”
As reported in the news, higher than normal levels of both iodine-131 and caesium-137 have been noted not only in Japan but worldwide due to the Fukushima incident. And plutonium has been found in soil samples near the reactor sites.
According to the On 30 March, deposition of iodine-131 was detected in 8 prefectures, and deposition of cesium-137 in 12 prefectures. On 30 March in the prefectures where deposition of iodine-131 was reported, the range was from 2.5 to 240 becquerel per square metre. For caesium-137, the range was from 3 to 57 becquerel per square metre. In the Shinjyuku district of Tokyo, the daily deposition of both iodine-131 and cesium-137 on 30 March was below 30 becquerel per square metre. — Since our briefing of yesterday, significant data related to food contamination has been submitted by the Japanese Ministry of Health, Labour and Welfare. Seventy-six samples were taken from 28-30 March, and reported on 30 March. Analytical results for 51 of the 76 samples for various vegetables, fruit (strawberry), seafood (sardines), and unprocessed raw milk in eight prefectures (Chiba, Fukushima, Gunma, Ibaraki, Kanagawa, Niigata, Saitama, and Yamagata), indicated that iodine-131, caesium-134 and caesium-137 were either not detected or were below the regulation values set by the Japanese authorities. However, it was reported that analytical results in Fukushima prefecture for the remaining 25 of the 76 samples for broccoli, cabbage, rapeseed, spinach and other leafy vegetables, indicated that iodine-131 and/or caesium-134 and caesium-137 exceeded the regulation values set by the Japanese authorities.”
Right now, as reported in the news, the biggest dangers from iodine-131 and caesium-137 due to the Fukushima situation are within a 100 kilometer distance of the power plant site, although levels significantly higher than normal have been reported elsewhere in Japan. Higher levels of these substances due to the Fukushima situation have also been observed in the US, both on the West and East coasts. These US levels are so-far significantly below those considered to offer health risks. As the damaged reactors and stored fuel rods continue to release large quantities of the radioactive substances, and because major new releases due to possible meltdowns could occur, however, the danger exists that the relatively comfortable situation in the US could change. And there is the danger of consuming contaminated vegetables or seafood anywhere it may be shipped to.
Biological impact from radiation damage due to ingested substances is different than radiation from sources outside the body in several important respects including: 1. Alpha and beta radiation is very short range so is of no threat when coming from substances outside the body unless those substances are touched, inhaled, eaten or otherwise penetrate the body and 2. Radiation from a substance like iodine-131 or caesium-137 that is absorbed in body tissues continues to create damage as long as that substance is within the body.
Consequences of radiation damage
Radiation damage can be short term or long term and is measured by exposure. Radiation dosages are measured in sieverts. “The sievert (symbol: Sv) is the SI derived unit of dose equivalent radiation. It attempts to quantitatively evaluate the biological effects of ionizing radiation as opposed to the physical aspects, which are characterised by the absorbed dose, measured in gray. It is named after Rolf Sievert, a Swedish medical physicist renowned for work on radiation dosage measurement and research into the biological effects of radiation(ref).”
This link contains a table relating exposure in sieverts to biological impacts. “Annual limit on intake (ALI) is the derived limit for the amount of radioactive material taken into the body of an adult worker by inhalation or ingestion in a year. ALI is the intake of a given radionuclide in a year that would result in:
- a committed effective dose equivalent of 0.05 Sv (5 rems) for a “reference human body”, or
- a committed dose equivalent of 0.5 Sv (50 rems) to any individual organ or tissue,
whatever dose is the smaller(ref).” The average natural radiation dose is 2.4 mSv per year, with a “typical range” reaching up to 10 mSv. As the table shows, a short-term dose of as little as 2 sieverts can lead to severe medical problems and a 5-50% chance of death even with medical care. And any dose of over 8 sieverts is sure to lead to rapid death.
The CDC has prepared a fact sheet Acute Radiation Syndrome (ARS): A Fact Sheet for the Public.
Longer-term exposure to even low intensities of radiation can lead to mutations of cell-cycle genes and cancers
Known protective measures can be taken when ingestion of one of the mentioned substances is unavoidable or has already happened. These are time-honored approaches known for decades. Specifically:
Potassium iodide for iodine-131
Absorption of iodine-131 can be significantly reduced or avoided by taking potassium iodide, though taking such pills after exposure to iodine-131 may be useless. A recent article in Pharmacy Practice News reports “As alarmed residents visit various Internet sites to purchase what is touted as a panacea for radiation sickness, costs of KI have skyrocketed. According to some reports, a package of 14 tablets that normally costs about $10 has soared to $540 in some ebay.com listings—a shocking 5,300% increase. Although some manufacturers are struggling to meet demands for KI in this suddenly lucrative market, others have simply given up, temporarily ceasing production.1-4” And this increase is in the US, not Japan. Further, the article reports “In situations where internal radiation contamination is suspected, the initial concern is inhalation of radioactive iodine, which is readily absorbed by the thyroid gland, leading to thyroid injury/cancer, particularly in infants/fetus, children and patients with low iodine stores. KI is known to flood the thyroid gland with stable iodine, preventing the organ from absorbing radioactive iodine—but it can only go so far. Consumers should be told that KI only protects the thyroid (not other parts of the body) from radioactive iodine—it cannot reverse effects of radioactive iodine once damage to the thyroid has occurred—and it cannot protect the body from radioactive elements other than radioactive iodine.5 — A dose of KI is recommended before or immediately following radiation exposure in all children and adults under the age of 40 years who are not allergic to iodine or shellfish, and if radiation still poses a threat 24 hours later, a repeat dose is administered (unless the patient is pregnant or breastfeeding, or a newborn infant).” Use of potassium iodide in other than emergency situations is definitely not recommended. You can see the document Prophylactic Use of Potassium Iodide (KI) in Radiological Emergencies – Information for Physicians.
Chelating Plutonium via DPTA
The 2005 publication Chelating agents used for plutonium and uranium removal in radiation emergency medicine points to an approach for removal of ingested plutonium. A chelating agent is one that chemically grabs molecules of an offending substance for transportation outside of the body. DPTA is a chelating agent that is approved by the FDA for removal of plutonium as well as americium, and curium which are also radioactive. The CDC document Facts About DTPA provides some basic information about the substance including: “DTPA is a kind of medicine called a chelating agent. Chelating agents work by binding and holding on to radioactive materials or poisons that get into the body. Once bound to a radioactive material or poison, the chelating agent is then passed from the body in the urine. Chelating agents help decrease the amount of time it takes to get a poison out of the body. — What does DTPA do? When radioactive materials get into the body through breathing, eating, drinking, or through open wounds, we say that “internal contamination” has occurred. Over the past 50 years, almost all cases of internal contamination have happened in people who use radioactive materials in their work. Since the 1960s, doctors have used DTPA as a chelating agent to treat internal contamination from radioactive materials such as americium, plutonium, californium, curium, and berkelium. Currently, DTPA is approved by the U.S. Food and Drug Administration (FDA) for chelation of only three radioactive materials: plutonium, americium, and curium. — What DTPA cannot do: Knowing what DTPA cannot do is also important. DTPA cannot bind all of the radioactive materials that might get into a person’s body after a radiological or nuclear event, such as a terrorist attack with a “dirty bomb.” This medicine cannot prevent radioactive materials from entering the body. DTPA cannot reverse the health effects caused by radioactive materials once these materials have entered the body. — How does DTPA work? DTPA comes in two forms: calcium (Ca-DTPA) and zinc (Zn-DTPA). Both forms work by tightly chelating (holding on to) plutonium, americium, and curium. These radioactive materials (bound to DTPA) are then passed from the body in the urine. When given within the first day after internal contamination has occurred, Ca-DTPA is about 10 times more effective than Zn-DTPA at chelating plutonium, americium, and curium. After 24 hours have passed, Ca-DTPA and Zn-DTPA are equally effective in chelating these radioactive materials. — How well does DTPA work? Chelating agents work best when given shortly after radioactive materials or poisons have entered the body. The more quickly a radioactive material or poison is removed from the body, the fewer and less serious the health effects will be. After 24 hours, plutonium, americium, and curium are harder to chelate. However, DTPA can still work to remove these radioactive materials from the body several days or even weeks after a person has been internally contaminated. — Who should get DTPA? Many people could be internally contaminated after a radiological or nuclear terrorist event. People contaminated with small amounts of radioactive materials might not need treatment with DTPA. Doctors and public health authorities will work together to decide who will likely benefit from DTPA treatment.” The literature related to plutonium chelation tends to be old with some articles going back 50 years or more(ref).
Clearing Caesium-137 with Prussian Blue
The CDC fact sheet Prussian blue tells the story: “Prussian blue can remove certain radioactive materials from people’s bodies, but must be taken under the guidance of a doctor. — People may become internally contaminated (inside their bodies) with radioactive materials by accidentally ingesting (eating or drinking) or inhaling (breathing) them, or through direct contact (open wounds). The sooner these materials are removed from the body, the fewer and less severe the health effects of the contamination will be. Prussian blue is a substance that can help remove certain radioactive materials from people’s bodies. However, small amounts of contamination may not require treatment. Doctors can prescribe Prussian blue if they determine that a person who is internally contaminated would benefit from treatment. — What Prussian blue is: Prussian blue was first produced as a blue dye in 1704 and has been used by artists and manufacturers ever since. It got its name from its use as a dye for Prussian military uniforms. Prussian blue dye and paint are still available today from art supply stores. — People SHOULD NOT take Prussian blue artist’s dye in an attempt to treat themselves. This type of Prussian blue is not designed to treat radioactive contamination and is not made for that purpose. People who are concerned about the possibility of being contaminated with radioactive materials should go to their doctors for advice and treatment. – Use of Prussian blue to treat radioactive contamination: Since the 1960s, Prussian blue has been used to treat people who have been internally contaminated with radioactive cesium (mainly Cs-137) and nonradioactive thallium (once an ingredient in rat poisons). Doctors can prescribe Prussian blue at any point after they have determined that a person who is internally contaminated would benefit from treatment. Prussian blue will help speed up the removal of cesium and thallium from the body. –How Prussian blue works: Prussian blue traps radioactive cesium and thallium (mainly Tl-201) in the intestines and keeps them from being re-absorbed by the body. The radioactive materials then move through the intestines and are excreted (passed) in bowel movements. Prussian blue reduces the biological half-life1 of cesium from about 110 days to about 30 days. Prussian blue reduces the biological half-life of thallium from about 8 days to about 3 days. Because Prussian blue reduces the time that radioactive cesium and thallium stay in the body, it helps limit the amount of time the body is exposed to radiation. — Who can take Prussian blue/ The drug is safe for most adults, including pregnant women, and children (2 â”€12 years). Dosing for infants (ages 0 â”€2 years) has not been determined yet. Women who are breast feeding their babies should stop breast feeding if they think they are contaminated with radioactive materials and consult with their doctors. People who have had constipation, blockages in the intestines, or certain stomach problems should be sure to tell their doctors before taking Prussian blue. Before taking Prussian blue, people also should be sure to tell their doctors about any other medicine they are taking. — How Prussian blue is given: Prussian blue is given in 500-milligram capsules that can be swallowed whole. People who cannot swallow pills can take Prussian blue by breaking the capsules and mixing the contents in food or liquid. Breaking open the capsules will cause people’s mouths and teeth to be blue during the time of treatment. — The dose of Prussian blue depends on the person’s age and the amount of contamination in the body. Prussian blue usually is given 3 times a day for a minimum of 30 days, depending on the extent of the contamination. – Warning: People SHOULD NOT take Prussian blue artist’s dye in an attempt to treat themselves. This type of Prussian blue is not designed to treat radioactive contamination and is not made for that purpose. People who are concerned about the possibility of being contaminated with radioactive materials should go to their doctors for advice and treatment.”
Taking antioxidants to minimize radiation damage
The above treatments are directed to elimination of dangerous radioactive substances from the body and may constitute a first level of defense in case of ingestion of radioactive substances through breathing, eating, drinking or exposure of open wounds. As recommended by the CDC they should be undertaken only under the guidance of a physician. Even using these approaches, however, the various radioactive substances will be resident in the body for a certain period and can possibly create serious damage depending on exposure dose and how quickly the removal action is initiated. There is a second level and complimentary of defense possible, and that is to minimize the damaging biological impact of radiation through taking a regimen of antioxidants.
I have written about the use of antioxidants to protect against the negative effects of medical imaging radiation first in a 2008 position paper Protection Against Radiation – The Second Line of Defense, and also briefly in an August 2009 blog entry Medical radiation risk – you can do something about it. Medical imaging radiation usually originates from outside the body and is electromagnetic in nature making it akin to gamma radiation such as is generated by an X-ray machine or as exists in outer space. Many studies have shown that antioxidants can be protective against biological damage caused by such exterior-originated radiation. Many such studies are cited in my position paper and a few new ones are cited here below. Much of this work has been sponsored by NASA and has been concerned with safety in space of astronauts.
Would antioxidants also provide protection from in-body radiation sources such as iodine-131 or caesium-137? The mechanisms of radiation damage are the same. Ionizing radiation, whatever the source may be, knocks electrons loose from molecules producing free radicals. These free radicals can propagate producing secondary showers of free radicals, particularly when generated by high-energy photons from gamma radiation. Free radicals can generate multiple forms of damage including to tissue structures, body cell DNA, germ-line DNA and mitochondrial DNA. From my treatise on radiation and antioxidants: “Ionizing x-radiation in any quantities is potentially deleterious to health. Radiation ionizes oxygen to produce Reactive Oxygen Species (ROS) like OH which steal electrons from lipids in cell membranes, a process called lipid peroxidation. A chain of damaging events can be let loose from a single high-energy electron event as unstable fatty acid radicals propagating in tissues produce other unstable radicals. The result can be damage to DNA or mitochondrial DNA, mangled chromosomes, protein cross-linking, cell apoptosis, genetic mutations, mutated germ cells and other forms of cell havoc. Radiation damage can show up in many ways including skin erythema, hair loss, vascular damage, internal bleeding, cataracts, cancers, weakened immune systems, sterility, mutations in offspring, premature ageing and death. Cell DNA repair mechanisms are effective in correcting some radiation-induced damage but may themselves be compromised by radiation.”
Newer literature references re antioxidants for radiation protection
My treatise PROTECTION AGAINST RADIATION – - THE SECOND LINE OF DEFENSE, last updated in 2008, provides a thorough discussion of how antioxidants are radioprotective and cites 30 of some 110 applicable literature citations I came across up to that point. Also you can check on the 2008 publication Antioxidants Reduce Consequences of Radiation Exposure. The following are selected updates on relevant research as reported in Science Daily articles.
A March 2011 Science Daily story Antioxidant Formula Prior to Radiation Exposure May Prevent DNA Injury, Trial Suggests reports: “A unique formulation of antioxidants taken orally before imaging with ionizing radiation minimizes cell damage, noted researchers at the Society of Interventional Radiology’s 36th Annual Scientific Meeting in Chicago, Ill. In what the researchers say is the first clinical trial of its kind, as much as a 50 percent reduction in DNA injury was observed after administering the formula prior to CT scans. — People are 70 percent water, and X-rays collide with water molecules to produce free radicals (groups of atoms with an unpaired number of electrons that are dangerous when they react with cellular components, causing damage and even cell death) that can go on to do damage by direct ionization of DNA and other cellular targets, noted Murphy. The research team evaluated whether a special combination of antioxidants have an ability to neutralize these free radicals before they can do damage. — “Our intent was to develop an effective proprietary formula of antioxidants to be taken orally prior to exposure that can protect a patient’s DNA against free radical mediated radiation injury, and we have applied to patent this formulation and a specific dose strategy,” said Murphy. — The experiments measured DNA damage as a surrogate marker for DNA injury.”
A September 2008 Science Daily story Plant Antioxidant May Protect Against Radiation Exposure reports on research specifically concerned with identifying protective measures in case of a nuclear emergency: “Resveratrol, the natural antioxidant commonly found in red wine and many plants, may offer protection against radiation exposure, according to a study by the University of Pittsburgh School of Medicine. When altered with acetyl, resveratrol administered before radiation exposure proved to protect cells from radiation in mouse models.” – The study, led by Joel Greenberger, M.D., professor and chairman of the Department of Radiation Oncology at the University of Pittsburgh School of Medicine, is overseen by Pitt’s Center for Medical Countermeasures Against Radiation. The center is dedicated to identifying and developing small molecule radiation protectors and mitigators that easily can be accessed and administered in the event of a large-scale radiological or nuclear emergency. — “New, small molecules with radioprotective capacity will be required for treatment in case of radiation spills or even as countermeasures against radiological terrorism,” said Dr. Greenberger. “Small molecules which can be easily stored, transported and administered are optimal for this, and so far acetylated resveratrol fits these requirements well.” — “Currently there are no drugs on the market that protect against or counteract radiation exposure,” he added. “Our goal is to develop treatments for the general population that are effective and non-toxic. — Dr. Greenberger and his team are conducting further studies to determine whether acetylated resveratrol eventually can be translated into clinical use as a radioprotective agent. In 2004, this same team of researchers identified the drug JP4-039, which can be delivered directly to the mitochondria, the energy producing areas of cells. When this occurs, the drug assists the mitochondria in combating radiation-induced cell death. — The results of the research were presented during the American Society for Therapeutic Radiology and Oncology’s (ASTRO) 50th Annual Meeting in Boston.”
An October 2008 2009 story Herbal Tonic For Radiotherapy? Gingko Biloba Tree May Protect Cells From Radiation Damage reports on radioprotection provided by Gingko biloba against gamma radiation from caesium-137: ” Antioxidant extracts of the leaves of the Gingko biloba tree may protect cells from radiation damage, according to a study published in the International Journal of Low Radiation. — Chang-Mo Kang of the Korea Institute of Radiological and Medical Sciences in Taegu and colleagues are interested in the protective effects of well-known herbal remedies of which Gingko biloba is one. G. biloba is a unique tree species with no close living relatives and extracts of its leaves contain antioxidant compounds including glycosides and terpenoids known as ginkgolides and bilobalides. — These compounds are thought to protect cells from damage by free radicals and other reactive oxidizing species found in the body. These are generated continuously by the body’s normal metabolism, and in excess in some diseases or after exposure to pollution or radiation. They damage proteins, DNA and other biomolecules and left unchecked can kill cells. — As such, extracts of certain plants that contain antioxidants, including G. biloba, have attracted interest for their pharmacological activity. G. biloba is currently sold as a herbal supplement and there are numerous claims for health benefits, including the possibility of preventing the onset of dementia or Alzheimer’s disease. — Kang and colleagues have now collected human white blood cells, lymphocytes, from healthy donors aged 18 to 50 years. They treated half of these cells with commercially available G. biloba extract in the laboratory and doused the other half with salt solution as an experimental control. They then compared the effects of gamma radiation from radioactive cesium on the white blood cells compared to the untreated control samples. — The team uses a light microscope to look for lymphocytes undergoing programmed cell death, or apoptosis, as a result of radiation exposure. They found that there was a significant increase in apoptosis in the untreated cells compared with those treated with G. biloba extract. Almost a third of the untreated cells underwent apoptosis compared with approximately one in twenty of the treated cells. Parallel studies with laboratory mice also demonstrated a similar protective effect against radiation poisoning. — The results suggest that the extracts can neutralize the free-radicals and oxidizing agents produced in the cells by the radiation and so prevent them from undergoing apoptosis.”
The July 2009 Science Daily story New Pill May Prevent Injury After Radiation Exposure reports “Researchers from Boston University School of Medicine (BUSM) and collaborators have discovered and analyzed several new compounds, collectively called the ”EUK-400 series,” which could someday be used to prevent radiation-induced injuries to kidneys, lungs, skin, intestinal tract and brains of radiological terrorism victims. The findings, which appear in the June issue of the Journal of Biological Inorganic Chemistry, describe new agents which can be given orally in pill form, which would more expedient in an emergency situation. — These agents are novel synthetic “antioxidants” that protect tissues against the kind of damage caused by agents such as “free radicals.” Free radicals, and similar toxic byproducts formed in the body, are implicated in many different types of tissue injury, including those caused by radiation exposure. Often, this kind of injury occurs months to years after radiation exposure. The BUSM researchers and their colleagues are developing agents that prevent injury even when given after the radiation exposure. — This paper describes a newer class of compounds, the ”EUK-400 series,” that are designed to be given as a pill. According to the researchers, experiments described in their paper prove that these agents are orally active. They also show that the new agents have several desirable “antioxidant” activities, and protect cells in a “cell death” model. — These same BUSM researchers and collaborators had previously discovered novel synthetic antioxidants that effectively mitigate radiation injuries, but had to be given by injection. “We have developed some of these agents and have studied them for over 15 years beginning with our work at the local biotechnology company Eukarion,” said senior author Susan Doctrow, PhD, a research associate professor of medicine at BUSM’s Pulmonary Center. “These injectible antioxidants are very effective, but there has also been a desire to have agents that can be given orally. A pill would be more feasible than an injection to treat large numbers of people in an emergency scenario,” she adds.”
The 2007 article Antioxidants Could Provide All-Purpose Radiation Protection reports “Two common dietary molecules found in legumes and bran could protect DNA from the harmful effects of radiation, researchers from the University of Maryland report. Inositol and inositol hexaphosphate (IP6) protected both human skin cells and a skin cancer-prone mouse from exposure to ultraviolet B (UVB) radiation, the damaging radiation found in sunlight, the team reported November 5 at the American Association for Cancer Research Centennial Conference on Translational Cancer Medicine. — According to the researchers, inositol and IP6 could decrease the severity of side effects from radiation therapy, saving healthy cells while simultaneously increasing the potency of the treatment against cancer cells. Both molecules are potent antioxidants, the Maryland researchers say, capable of preventing reactive molecules from injuring DNA and turning cells cancerous. — “Both of these potent antioxidants have been shown to have broad-spectrum anti-tumor capabilities, and now our studies confirm the degree to which these molecules protect against the DNA-damaging effects of ionizing radiation,” said Abulkalam M. Shamsuddin, M.D., professor of pathology at the University of Maryland School of Medicine. “Radiation damage is radiation damage, regardless of the source, so there could also be a protective role for IP6 in any form of radiation exposure, whether it is from a therapeutic dose or from solar, cosmic or nuclear sources.” – Normally, cells permanently damaged by radiation undergo a genetically programmed process of cell suicide, called apoptosis. Shamsuddin reports that UVB-irradiated human keratinocytes, when treated with IP6, were more likely to survive. Untreated skin cells were more likely to undergo apoptosis, indicating that the DNA in those cells was damaged irreparably and fatally. According to Shamsuddin, the treated cells take an extended pause at the point in the cellular life cycle where innate mechanisms repair DNA before the cell divides. — “IP6 certainly has some interactivity with DNA, but how exactly it works to repair DNA is still something of a mystery. There are reports that IP6 binds with DNA repair molecule Ku to bring about the repair process,” Shamsuddin said. — According to Shamsuddin, IP6 could also offer protection against accidents or purposeful incidents involving nuclear material. “It could also be advisable to use IP6 plus inositol as a cautionary treatment following a nuclear disaster or dirty bomb,” Shamsuddin said.”
Drugs under development that mitigate radiation damage
The April 2009 story Developmental Drug Helps Protect Against Radiation Damage reports “The study, led by Joel Greenberger, M.D., professor and chairman of the Department of Radiation Oncology at Pitt, is overseen by Pitt’s Center for Medical Countermeasures Against Radiation. The center is dedicated to identifying and developing small molecule radiation protectors and mitigators that can be easily accessed and administered in the event of a large-scale radiological or nuclear emergency. — JP4-039 assists the mitochondria, the energy generator of all cells, in combating irradiation-induced cell death. For this study, cells treated immediately after irradiation with JP4-039 demonstrated significant radioprotection, suggesting a potential role for the drug as a mitigator of radiation damage. — “Currently, no drugs on the market counteract the effects of radiation exposure,” said Dr. Greenberger. “We know this drug can counteract the damage caused by irradiation, and now we want to develop the ideal dosage, one that is effective for the general population while remaining non-toxic. Our goal is to take this drug through a phase I clinical trial and, once the dosage is established, develop the drug for late-stage clinical trials and market licensing.” — The study, led by Joel Greenberger, M.D., professor and chairman of the Department of Radiation Oncology at Pitt, is overseen by Pitt’s Center for Medical Countermeasures Against Radiation. The center is dedicated to identifying and developing small molecule radiation protectors and mitigators that can be easily accessed and administered in the event of a large-scale radiological or nuclear emergency. — JP4-039 assists the mitochondria, the energy generator of all cells, in combating irradiation-induced cell death. For this study, cells treated immediately after irradiation with JP4-039 demonstrated significant radioprotection, suggesting a potential role for the drug as a mitigator of radiation damage. — “Currently, no drugs on the market counteract the effects of radiation exposure,” said Dr. Greenberger. “We know this drug can counteract the damage caused by irradiation, and now we want to develop the ideal dosage, one that is effective for the general population while remaining non-toxic. Our goal is to take this drug through a phase I clinical trial and, once the dosage is established, develop the drug for late-stage clinical trials and market licensing.”
The 2008 story Could a Nanotube-Based Drug Prevent Radiation Injury? reports “The Department of Defense has commissioned a nine-month study from Rice University chemists and scientists in the Texas Medical Center to determine whether a new drug based on carbon nanotubes can help prevent people from dying of acute radiation injury following radiation exposure. The new study was commissioned after preliminary tests found the drug was greater than 5,000 times more effective at reducing the effects of acute radiation injury than the most effective drugs currently available. — “More than half of those who suffer acute radiation injury die within 30 days, not from the initial radioactive particles themselves but from the devastation they cause in the immune system, the gastrointestinal tract and other parts of the body,” said James Tour, Rice’s Chao Professor of Chemistry, director of Rice’s Carbon Nanotechnology Laboratory (CNL) and principal investigator on the grant. “Ideally, we’d like to develop a drug that can be administered within 12 hours of exposure and prevent deaths from what are currently fatal exposure doses of ionizing radiation.” — The drug is based on single-walled carbon nanotubes, hollow cylinders of pure carbon that are about as wide as a strand of DNA. To form NTH, Rice scientists coat nanotubes with two common food preservatives — the antioxidant compounds butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) — and derivatives of those compounds. — “The same properties that make BHA and BHT good food preservatives, namely their ability to scavenge free radicals, also make them good candidates for mitigating the biological affects that are induced through the initial ionizing radiation event,” Tour said. — In preliminary tests at M.D. Anderson in July 2007, mice showed enhanced protection when exposed to lethal doses of ionizing radiation when they were given first-generation NTH drugs prior to exposure.”
Wrapping it up
1. By far, the best protection against nuclear radiation is avoiding it.
2. We do not know when the release of radioactive substances into the environment from the earthquake and tsunami-struck Fukushima Daiichi nuclear power plant in Japan will stop. So far, efforts to bring the situation under control have not succeeded.
3. Two radioactive substances of particular concern are iodine-131 and caesium-137. These have already been released into the environment in large quantities due to the Fukushima disaster. These substances are both highly radioactive and highly bioactive, being readily absorbed into human bodies. Also of serious concern is plutonium, an extremely toxic byproduct of nuclear fission that has been found in the ground near the reactor sites.
4. Consequences from internal exposure to these substances can be most serious both in the short and long term. Each of these substances in critical doses can cause death if left lodged in the body.
5. Radiation from ingested radioactive substances originating from a nuclear accident is in some respects similar to radiation received from external sources, in some respects different. The big dangers from of iodine-131, caesium-137 or plutonium come into play if they are absorbed into the body via breathing, eating or drinking them. Caesium-137, for example, is readily absorbed from soil into certain vegetables and can enter the body effectively by eating such contaminated vegetables.
6. Traditional means exist for removing these substances from bodies or preventing their absorption including use of potassium iodide, Prussian blue, and DPTA. These approaches should be pursued only under medical supervision.
7. Effectively removing or preventing adsorption of iodine-131, caesium-137 or plutonium using these approaches takes time, may be only partially effective, and may still leave the result of substantial radiation injury under the best of circumstances.
8. Antioxidants have been shown to be at least partially effective in reducing the damaging effects of radiation from external sources. The known mechanisms of radiation damage suggests that the same should be the case for radiation from ingested sources.
9. Research studies have established that a number of conventional antioxidants are protective against internal radiation damage including but not limited to resveratrol, alpha-lipoic acid, ginko biloba, beta carotene, curcumin, inositol, selenium, melatonin, vitamin C, vitamin E, N-acetylcysteine and ginseng(ref)(ref)(ref).
10. A number of new antioxidant and antioxidant combinations as well as other substances are being investigated for their superior abilities to protect against radiation. How their effectiveness compares against that of conventional antioxidants is unknown.