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"The effects of radiation on the human body"
(March 2017)
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by Dr. Shinya Matsuura
Director, Research Institute for Radiation Biology
and Medicine, Hiroshima University
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Introduction
Over seventy years have passed since the atomic bomb was dropped on Hiroshima on August 6, 1945.
President Obama of the United States, the country that dropped the bomb, was the first sitting US president to visit Hiroshima, and the date of his visit, May 27, 2016, became an historical date for humankind.
In his speech, Obama referred to the dual nature of science and technology.
He spoke of the fact that progress in science and technology needs to be accompanied by social progress, and that if science and technology move ahead alone then they may bring destruction to humankind―he said that this is what the bombing of Hiroshima taught us.
The most significant feature of the atomic bomb is that large amounts of radiation, which do not occur with regular bombs, are emitted on the surface of the ground, and this causes damage to people when they are exposed to it.
In this article, I aim in particular to provide a commentary on the effects of radiation on the human body.
Acute damage and late-onset damage
Acute damage appears when a person has been exposed to a large amount of radiation.
Acute damage is divided into four phases: the prodromal phase, the incubation phase, the onset phase and the recovery phase.
Within 48 hours of being exposed to radiation, early symptoms appear via the paths of the autonomic nervous system, including whole body faintness, nausea and vomiting, and this period is known as the prodromal period.
The higher the dosage of radiation, the faster the early symptoms appear, and with small dosages of radiation sometimes there are no clear symptoms.
After this, a period with no symptoms other than weariness and fatigue appears―this is called the incubation period.
This is because cells that have resistance to the radiation have survived and are functioning.
From around the third week through to two months, there are symptoms such as hair loss, oral inflammation, and hematopoietic damage causing weakening of the immune system and a tendency to bleed, and gastrointestinal tract disturbance leading to vomiting and diarrhea.
The combination of these symptoms then causes serious infections, vomiting of blood and melena.
This period is known as the onset period.
Cells that have been exposed to radiation have an abnormality in the division of cells, which means that tissue or organs that have active cell division are particularly weak and highly sensitive to radiation.
Some parts of tissue have particularly active cell division, and include stem cells.
Stem cells are the cells that form the origin of cells that make up tissue, and when one stem cell divides, one of the two cells that is created remains as a stem cell, while the other cell becomes one of the tissue cells.
Stem cells are particularly weak and sensitive to radiation.
The skin is highly sensitive to radiation.
The surface of the skin is made up of three layers: the epidermis, the dermis, and the hypodermal tissue.
Stem cells are found in the deepest part of the epidermis, and are damaged when the skin is exposed to radiation.
Symptoms such as red patches, hair loss, blistering and skin ulcers will form depending on the radiation dosage.
When the dosage is high, necrosis (dead skin) may also occur.
The small intestine is also highly sensitive to radiation.
The inner lumen of the small intestine is covered in fine projections called small-intestinal villi.
Between the small-intestinal villi are
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concave parts called crypts, and stem cells are found at the bottom of the crypts (Fig.1).
Stem cells and the newly-born young cells divide, differentiate into cells that control digestion absorption, and gradually move upwards to form villi.
When the small intestine is exposed to large amounts of radiation, the stem cells and young cells that are in the crypts are damaged, and villi cannot be adequately formed.
This leads to loss of the digestion and absorption function in the small intestine, causing diarrhea and melena.
Hematopoietic stem cells are also highly sensitive to radiation.
Bone
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marrow has many hematopoietic stem cells, which make erythrocytes, white blood cells and platelets.
When bone marrow is exposed to radiation, first the number of lymphocytes is reduced, then white blood cells and platelets are reduced.
When lymphocytes are reduced, the person has weakened immunity against viruses and other diseases.
When white blood cells are reduced, the person becomes more prone to infectious diseases including bacteria.
When platelets are reduced, it becomes harder to stop bleeding.
Three months after exposure to radiation, there are signs of recovery from radiation damage.
This is known as the recovery period.
A while after the symptoms of acute damage have healed, late-onset disorders appear.
A typical example is cancer.
In the atomic bombing of Hiroshima and Nagasaki, there were many
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cases of leukemia that started after the incubation period of 6-7 years after the bombing (Fig.2).
After leukemia peaked, there was an increase in solid tumors, depending on radiation dosage, with an incubation period of 10-40 years.
Over seventy years have passed since the bombing, but even today it is well known that hibakusha have a high risk of developing solid tumors.
Deterministic effects and stochastic effects
The biological effects of radiation may be divided into the deterministic effects and the stochastic effects (Fig.3).
Deterministic effects include radiation-caused cataracts, hematopoietic disorders and gastrointestinal tract disturbances.
There is a threshold for deterministic effects, and there is no impact if the dosage of the radiation exposed to is below the threshold.
Exposure to radiation above the threshold leads to illness.
In a graph with the dosage of radiation on the horizontal axis and the frequency of illness on the vertical axis, the deterministic effects will form an S-curve as shown in the upper graph in Fig.3.
This indicates that anyone who is
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exposed to radiation above a certain level will become ill.
On the other hand, cancer, which is one of the typical late-onset illnesses, can be categorized as stochastic effects.
For deterministic effects, the risk of developing illness increases as the dosage of radiation increases.
In the case of solid tumors, the frequency of development of symptoms increases in a straight line as indicated in the lower graph in Fig.3.
When there is a threshold, the radiation dosage is controlled so that radiation damage does not occur.
On the other hand, in terms of radiation protection, the International Commission on Radiological Protection (ICRP) believes that there is no threshold for cancer caused by radiation.
This is known as the Linear Non-Threshold (LNT) hypothesis.
The hypothesis states that even if the radiation dosage is low there is still a risk of cancer.
Therefore, it is necessary to keep the radiation exposure below the acceptable level.
However, as will be stated below, for the stochastic effects of cancer, there are still many issues, in particular at the low dosage level.
Radiation disorder mechanism
Messenger RNA is translated from genomic DNA in cells and transcribed into amino acid sequences.
This is an essential process used to make the various types of protein that make up the human body.
Radiation harms the various biomolecules that form the human body; in particular, when both strands of the DNA double helix are cut the cells are impacted.
In response to this, cells have the ability to repair damaged DNA, which means that DNA damage caused by
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radiation is repaired to its original state by repair protein.
Fig.4 shows nucleus of a cell using immunofluorescent staining technique.
It shows that in the cell exposed to radiation, the repair protein forms a yellow-green colored nuclear foci (on printed paper this appears as white. A color photograph will be put in the online version).
Within this foci, the damaged DNA will be repaired to its original state.
DNA damage that was caused by a small dosage of radiation was repaired to its original state by the cells' repair protein and the cells are maintained normally.
On the other hand, when the dosage of radiation is large, the DNA has multiple wounds, and as the multiple damages, and then DNA repair errors are accumulated (Fig.5).
When there is a build-up of DNA repair errors, the cells die.
As a result, there is deterioration of the functioning of organs and tissue that are sensitive to radiation, and this causes acute damage.
On the other hand, sometimes cells survive even while experiencing DNA repair errors.
In such cases, there is an accumulation of abnormalities in the DNA genes, and these may become cancer cells.
This is said to be the mechanism for late-onset cancer.
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Effects of low dosages and low dose rates of radiation
As stated above, when there is exposure to a large amount of radiation all at once acute symptoms will definitely appear, and there is an increased risk of cancer later.
On the other hand, there are different interpretations on the risk of cancer when radiation dose is lower than
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100mSv (Fig.6).
The ICRP proposes the LNT hypothesis, which states that there is a health risk no matter how low the dosage of radiation is, and this is supported by many researchers as a protective model that stands on the side of safety in terms of protecting people.
However, it has been controversial whether the actual impact would be linear.
Some people believe that there would be no health risk at low dosages because of DNA's repair ability, while the others believe that there would be a higher risk of cancer at low radiation dosages because damaged cells would also have an effect on surrounding cells
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that had not been exposed to radiation.
In the current approach to defense against radiation, risk to health is estimated based on the cumulative dosage of radiation to which a person has been exposed.
However, we know that even if the dosage of radiation is the same, differences in the time that the person is exposed to the radiation lead to different biological effects.
In other words, low dosage can be divided into two categories: low dosage at a high dose rate and low dosage at a low dose rate.
A typical example of low dosage at a high dose rate is exposure to medical radiation experienced when using x-rays or CT scans.
On the other hand, low dosage at a low dose rate refers to cases where a low dosage of radiation is experienced for a long period of time, which may then cumulate as a high dosage.
Some examples of this are international plane flights and regions where naturally occurring radiation is high.
The risk of contracting cancer from radiation has been estimated based on epidemiological surveys conducted in Hiroshima and Nagasaki, but there are different opinions as to whether the high dosage, ultra-high dose rate data should be applied uniformly to low dosages of radiation.
Just as the extent of landslides differs depending on whether the rain is torrential or light, it is thought that there is also a possibility that biological effects differ depending on whether it is low dosage at a high dose rate or low dosage at a low dose rate.
This is the one of the important issues that needs to be resolved in the future.
Even in large-scale research on atomic bomb epidemiology, the biological effect of low radiation dosage of less than 100mSv has not been clarified.
For this reason, a breakthrough is needed on the assessment of the effect of low radiation dosage at low dose rates based on scientific evidence.
The Hiroshima University Institute for Radiation Biology and Medicine, the Nagasaki University Atomic Bomb Disease Institute, and the Fukushima Medical University Fukushima Global Medical Science Center applied jointly to the Network-type Joint Usage/Research Center for Radiation Disaster Medical Science, and received certification from the Ministry of Education, Culture, Sports, Science and Technology.
The three universities (Hiroshima University Institute for Radiation Biology and Medicine is the hub) started joint usage and joint research activities from April 2016, and are working on research topics together, including the effect and risk of low dosages of radiation.
In conclusion
As a university that operates in Hiroshima, a city hit by the atomic bomb, Hiroshima University has as its mission the development of human resources who strive for peace.
To this end, the university provides Hiroshima University students with opportunities to think about peace through its Peace Science Courses.
I teach one of the classes in this course: War and Peace from the Viewpoint of Medicine.
As a new initiative, Hiroshima University works together with Hiroshima Peace Culture Foundation to conduct academic surveys and research, and in December 2016, Hiroshima University President Mitsuo Ochi and Hiroshima Peace Culture Foundation Chairperson Yasuyoshi Komizo signed an agreement at Hiroshima University.
According to this agreement, both organizations will work towards strengthening their ties, by enhancing peace education for Hiroshima University students, increasing the collections of A-bomb-related materials at the Hiroshima Peace Memorial Museum, conducting joint research and more.
The agreement also states that the organizations will examine initiatives to share A-bombed artifacts held by Hiroshima Peace Culture Foundation and Hiroshima University Institute for Radiation Biology and Medicine, and jointly create digital and archived records of A-bombed artifacts that are severely deteriorated, aiming for a reevaluation of such artifacts.
Hiroshima University Institute for Radiation Biology and Medicine would like to convey its desire for peace to the people of the world through such activities.
【References】
1. Handbook on Effects of A-Bomb Radiation Second Revision (Ed. Hiroshima International
Council for Health Care of the Radiation-exposed) (Bunkodo Co., Ltd., May 2012)
2. Let’s Learn About the Basics of Radiation (by Osamu Yamamoto) (Bungeisha Co., Ltd., June
2016)
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Profile
[Shinya Matsuura]
1979/04, 1985/03, Yamaguchi University, Faculty of Medicine, Japan
1986/04, 1990/03, Yamaguchi University, Graduate School, Division of Medicine, Japan
1991/04, 1993/03, Japan Society for the Promotion of Science for Japanese Junior Scientists, Fellow
1993/08, 1995/07, St. Mary's Hospital Medical School, University of London, Visiting Scientist
1995/08, 1999/03, RIRBM, Hiroshima University, Research associate
1999/04, 2002/07, RIRBM, Hiroshima University, Assistant professor
2002/08, RIRBM, Hiroshima University, Professor
2016/01, RIRBM, Hiroshima University, Director
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