Radiobiology

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Radiobiology (also known as radiation biology) is a field of clinical and basic medical sciences that involves the study of the action of ionizing radiation on living things, especially health effects of radiation. Ionizing radiation is generally harmful and potentially lethal to living things but can have health benefits in radiation therapy for the treatment of cancer and thyrotoxicosis. Its most common impact is the induction of cancer with a latent period of years or decades after exposure. High doses can cause visually dramatic radiation burns, and/or rapid fatality through acute radiation syndrome. Controlled doses are used for medical imaging and radiotherapy.

Ionizing radiation Radiation that carries enough light energy to liberate electrons from atoms or molecules

Ionizing radiation is radiation that carries sufficient energy to detach electrons from atoms or molecules, thereby ionizing them. Ionizing radiation is made up of energetic subatomic particles, ions or atoms moving at high speeds, and electromagnetic waves on the high-energy end of the electromagnetic spectrum.

Radiation therapy therapy using ionizing radiation

Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is therapy using ionizing radiation, generally as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radiation therapy may be curative in a number of types of cancer if they are localized to one area of the body. It may also be used as part of adjuvant therapy, to prevent tumor recurrence after surgery to remove a primary malignant tumor. Radiation therapy is synergistic with chemotherapy, and has been used before, during, and after chemotherapy in susceptible cancers. The subspecialty of oncology concerned with radiotherapy is called radiation oncology.

Up to 10% of invasive cancers are related to radiation exposure, specifically ionizing radiation. Additionally, the vast majority of non-invasive cancers are non-melanoma skin cancers caused by ultraviolet radiation. Ultraviolet's position on the electromagnetic spectrum is on the boundary between ionizing and non-ionizing radiation. Non-ionizing radio frequency radiation from mobile phones, electric power transmission, and other similar sources have been described as a possible carcinogen by the World Health Organization's International Agency for Research on Cancer, but the link remains unproven.

Contents

Health effects

In general, ionizing radiation is harmful and potentially lethal to living beings but can have health benefits in radiation therapy for the treatment of cancer and thyrotoxicosis.

Most adverse health effects of radiation exposure may be grouped in two general categories:

Stochastic

Some effects of ionizing radiation on human health are stochastic, meaning that their probability of occurrence increases with dose, while the severity is independent of dose. [2] Radiation-induced cancer, teratogenesis, cognitive decline, and heart disease are all examples of stochastic effects.

Stochastic refers to a randomly determined process. The word first appeared in English to describe a mathematical object called a stochastic process, but now in mathematics the terms stochastic process and random process are considered interchangeable. The word, with its current definition meaning random, came from German, but it originally came from Greek στόχος (stókhos), meaning 'aim, guess'.

Its most common impact is the stochastic induction of cancer with a latent period of years or decades after exposure. The mechanism by which this occurs is well understood, but quantitative models predicting the level of risk remain controversial. The most widely accepted model posits that the incidence of cancers due to ionizing radiation increases linearly with effective radiation dose at a rate of 5.5% per sievert. [3] If this linear model is correct, then natural background radiation is the most hazardous source of radiation to general public health, followed by medical imaging as a close second. Other stochastic effects of ionizing radiation are teratogenesis, cognitive decline, and heart disease.

Sievert SI derived unit of equivalent dose of ionizing radiation

The sievert is a derived unit of ionizing radiation dose in the International System of Units (SI) and is a measure of the health effect of low levels of ionizing radiation on the human body. The sievert is of importance in dosimetry and radiation protection, and is named after Rolf Maximilian Sievert, a Swedish medical physicist renowned for work on radiation dose measurement and research into the biological effects of radiation.

Linear no-threshold model

The linear no-threshold model (LNT) is a model used in radiation protection to quantify radiation exposure and set regulatory limits. It is most frequently used to calculate the probability of radiation-induced cancer at both high doses where epidemiology studies support its application but, controversially, it likewise finds applications in calculating the effects of low doses, a dose region that is fraught with much less statistical confidence in its predictive power but that nonetheless has resulted in major personal and policy decisions in regards to public health. The model assumes that the long-term, biological damage caused by ionizing radiation is directly proportional to the dose. This allows the summation by dosimeters of all radiation exposure, without taking into consideration dose levels or dose rates. In other words, radiation is always considered harmful with no safety threshold, and the sum of several very small exposures are considered to have the same effect as one larger exposure.

Radiation-induced cognitive decline describes the possible correlation between radiation therapy and mild cognitive impairment. Radiation therapy is used mainly in the treatment of cancer. Radiation therapy can be used to cure care or shrink tumors that are interfering with quality of life. Sometimes radiation therapy is used alone; other times it is used in conjunction with chemotherapy and surgery. For people with brain tumors, radiation can be an effective treatment because chemotherapy is often less effective due to the blood–brain barrier. Unfortunately for some patients, as time passes, people who received radiation therapy may begin experiencing deficits in their learning, memory, and spatial information processing abilities. The learning, memory, and spatial information processing abilities are dependent on proper hippocampus functionality. Therefore, any hippocampus dysfunction will result in deficits in learning, memory, and spatial information processing ability.

Quantitative data on the effects of ionizing radiation on human health is relatively limited compared to other medical conditions because of the low number of cases to date, and because of the stochastic nature of some of the effects. Stochastic effects can only be measured through large epidemiological studies where enough data has been collected to remove confounding factors such as smoking habits and other lifestyle factors. The richest source of high-quality data comes from the study of Japanese atomic bomb survivors. In vitro and animal experiments are informative, but radioresistance varies greatly across species.

Radioresistance is the level of ionizing radiation that organisms are able to withstand.

The added lifetime risk of developing cancer by a single abdominal CT of 8 mSv is estimated to be 0.05%, or 1 one in 2,000. [4]

Deterministic

Deterministic effects are those that reliably occur above a threshold dose, and their severity increases with dose. [2]

High radiation dose gives rise to deterministic effects which reliably occur above a threshold, and their severity increases with dose. Deterministic effects are not necessarily more or less serious than stochastic effects; either can ultimately lead to a temporary nuisance or a fatality. Examples of deterministic effects are:

The US National Academy of Sciences Biological Effects of Ionizing Radiation Committee "has concluded that there is no compelling evidence to indicate a dose threshold below which the risk of tumor induction is zero" [5]

PhaseSymptomWhole-body absorbed dose (Gy)
1–2  Gy 2–6  Gy 6–8  Gy 8–30  Gy > 30  Gy
Immediate Nausea and vomiting 5–50%50–100%75–100%90–100%100%
Time of onset2–6 h1–2 h10–60 min< 10 minMinutes
Duration< 24 h24–48 h< 48 h< 48 hN/A (patients die in < 48 h)
Diarrhea NoneNone to mild (< 10%)Heavy (> 10%)Heavy (> 95%)Heavy (100%)
Time of onset3–8 h1–3 h< 1 h< 1 h
Headache SlightMild to moderate (50%)Moderate (80%)Severe (80–90%)Severe (100%)
Time of onset4–24 h3–4 h1–2 h< 1 h
Fever NoneModerate increase (10–100%)Moderate to severe (100%)Severe (100%)Severe (100%)
Time of onset1–3 h< 1 h< 1 h< 1 h
CNS functionNo impairmentCognitive impairment 6–20 hCognitive impairment > 24 hRapid incapacitation Seizures, tremor, ataxia, lethargy
Latent period 28–31 days7–28 days< 7 daysNoneNone
Illness Mild to moderate Leukopenia
Fatigue
Weakness
Moderate to severe Leukopenia
Purpura
Hemorrhage
Infections
Alopecia after 3  Gy
Severe leukopenia
High fever
Diarrhea
Vomiting
Dizziness and disorientation
Hypotension
Electrolyte disturbance
Nausea
Vomiting
Severe diarrhea
High fever
Electrolyte disturbance
Shock
N/A (patients die in < 48h)
MortalityWithout care0–5%5–95%95–100%100%100%
With care0–5%5–50%50–100%99–100%100%
Death6–8 weeks4–6 weeks2–4 weeks2 days – 2 weeks1–2 days
Table Source [6]

By type of radiation

When alpha particle emitting isotopes are ingested, they are far more dangerous than their half-life or decay rate would suggest. This is due to the high relative biological effectiveness of alpha radiation to cause biological damage after alpha-emitting radioisotopes enter living cells. Ingested alpha emitter radioisotopes such as transuranics or actinides are an average of about 20 times more dangerous, and in some experiments up to 1000 times more dangerous than an equivalent activity of beta emitting or gamma emitting radioisotopes. If the radiation type is not known then it can be determined by differential measurements in the presence of electrical fields, magnetic fields, or varying amounts of shielding.

External dose quantities used in radiation protection. See article on sievert on how these are calculated and used. Dose quantities and units.png
External dose quantities used in radiation protection. See article on sievert on how these are calculated and used.

In pregnancy

The risk for developing radiation-induced cancer at some point in life is greater when exposing a fetus than an adult, both because the cells are more vulnerable when they are growing, and because there is much longer lifespan after the dose to develop cancer.

Possible deterministic effects include of radiation exposure in pregnancy include miscarriage, structural birth defects, Growth restriction and intellectual disability. [7] The determinstistic effects have been studied at for example survivors of the atomic bombings of Hiroshima and Nagasaki and cases where radiation therapy has been necessary during pregnancy:

Gestational age Embryonic age EffectsEstimated threshold dose (mGy)
2 to 4 weeks0 to 2 weeks Miscarriage or none (all or nothing)50 - 100 [7]
4 to 10 weeks2 to 8 weeksStructural birth defects 200 [7]
Growth restriction 200 - 250 [7]
10 to 17 weeks8 to 15 weeksSevere intellectual disability 60 - 310 [7]
18 to 27 weeks16 to 25 weeksSevere intellectual disability (lower risk)250 - 280 [7]

The intellectual deficit has been estimated to be about 25 IQ-points per 1,000 mGy at 10 to 17 weeks of gestational age. [7]

These effects are sometimes relevant when deciding about medical imaging in pregnancy, since projectional radiography and CT scanning exposes the fetus to radiation.

Also, the risk for the mother of later acquiring radiation-induced breast cancer seems to be particularly high for radiation doses during pregnancy. [8]

Measurement

The human body cannot sense ionizing radiation except in very high doses, but the effects of ionization can be used to characterize the radiation. Parameters of interest include disintegration rate, particle flux, particle type, beam energy, kerma, dose rate, and radiation dose.

The monitoring and calculation of doses to safeguard human health is called dosimetry and is undertaken within the science of health physics. Key measurement tools are the use of dosimeters to give the external effective dose uptake and the use of bio-assay for ingested dose. The article on the sievert summarises the recommendations of the ICRU and ICRP on the use of dose quantities and includes a guide to the effects of ionizing radiation as measured in sieverts, and gives examples of approximate figures of dose uptake in certain situations.

The committed dose is a measure of the stochastic health risk due to an intake of radioactive material into the human body. The ICRP states "For internal exposure, committed effective doses are generally determined from an assessment of the intakes of radionuclides from bioassay measurements or other quantities. The radiation dose is determined from the intake using recommended dose coefficients". [9]

Absorbed, equivalent and effective dose

The Absorbed dose is a physical dose quantity D representing the mean energy imparted to matter per unit mass by ionizing radiation. In the SI system of units, the unit of measure is joules per kilogram, and its special name is gray (Gy). [10] The non-SI CGS unit rad is sometimes also used, predominantly in the USA.

To represent stochastic risk the equivalent dose HT and effective dose E are used, and appropriate dose factors and coefficients are used to calculate these from the absorbed dose. [11] Equivalent and effective dose quantities are expressed in units of the sievert or rem which implies that biological effects have been taken into account. These are usually in accordance with the recommendations of the International Committee on Radiation Protection (ICRP) and International Commission on Radiation Units and Measurements (ICRU). The coherent system of radiological protection quantities developed by them is shown in the accompanying diagram.

Organizations

The International Commission on Radiological Protection (ICRP) manages the International System of Radiological Protection, which sets recommended limits for dose uptake. Dose values may represent absorbed, equivalent, effective, or committed dose.

Other important organizations studying the topic include

Exposure pathways

External

A schematic diagram showing a rectangle being irradiated by an external source (in red) of radiation (shown in yellow). Externalsource.svg
A schematic diagram showing a rectangle being irradiated by an external source (in red) of radiation (shown in yellow).
A schematic diagram showing a rectangle being irradiated by radioactive contamination (shown in red) which is present on an external surface such as the skin; this emits radiation (shown in yellow) which can enter the animal's body Contaminationonskin.svg
A schematic diagram showing a rectangle being irradiated by radioactive contamination (shown in red) which is present on an external surface such as the skin; this emits radiation (shown in yellow) which can enter the animal's body

External exposure is exposure which occurs when the radioactive source (or other radiation source) is outside (and remains outside) the organism which is exposed. Examples of external exposure include:

External exposure is relatively easy to estimate, and the irradiated organism does not become radioactive, except for a case where the radiation is an intense neutron beam which causes activation.

By type of medical imaging

Effective dose by medical imaging type
Target organsExam typeEffective dose in adults [12] Equivalent time of background radiation [12]
CT of the head Single series2 mSv8 months
With + without radiocontrast 4 mSv16 months
Chest CT of the chest 7 mSv2 years
CT of the chest, lung cancer screening protocol1.5 mSv6 months
Chest X-ray 0.1 mSv10 days
Heart Coronary CT angiography 12 mSv4 years
Coronary CT calcium scan 3 mSv1 year
Abdominal CT of abdomen and pelvis 10 mSv3 years
CT of abdomen and pelvis, low dose protocol3 mSv [13] 1 year
CT of abdomen and pelvis, with + without radiocontrast 20 mSv7 years
CT Colonography 6 mSv2 years
Intravenous pyelogram 3 mSv1 year
Upper gastrointestinal series 6 mSv2 years
Lower gastrointestinal series 8 mSv3 years
Spine Spine X-ray 1.5 mSv6 months
CT of the spine6 mSv2 years
Extremities X-ray of extremity 0.001 mSv3 hours
Lower extremity CT angiography 0.3 - 1.6 mSv [14] 5 weeks - 6 months
Dental X-ray 0.005 mSv1 day
DEXA (bone density)0.001 mSv3 hours
PET-CT combination25 mSv8 years
Mammography 0.4 mSv7 weeks

Internal

Internal exposure occurs when the radioactive material enters the organism, and the radioactive atoms become incorporated into the organism. This can occur through inhalation, ingestion, or injection. Below are a series of examples of internal exposure.

When radioactive compounds enter the human body, the effects are different from those resulting from exposure to an external radiation source. Especially in the case of alpha radiation, which normally does not penetrate the skin, the exposure can be much more damaging after ingestion or inhalation. The radiation exposure is normally expressed as a committed dose.

History

Although radiation was discovered in late 19th century, the dangers of radioactivity and of radiation were not immediately recognized. Acute effects of radiation were first observed in the use of X-rays when Wilhelm Röntgen intentionally subjected his fingers to X-rays in 1895. He published his observations concerning the burns that developed, though he misattributed them to ozone, a free radical produced in air by X-rays. Other free radicals produced within the body are now understood to be more important. His injuries healed later.

As a field of medical sciences, radiobiology originated from Leopold Freund's 1896 demonstration of the therapeutic treatment of a hairy mole using a new type of electromagnetic radiation called x-rays, which was discovered 1 year previously by the German physicist, Wilhelm Röntgen. After irradiating frogs and insects with X-rays in early 1896, Ivan Romanovich Tarkhanov concluded that these newly discovered rays not only photograph, but also "affect the living function". [16] At the same time, Pierre and Marie Curie discovered the radioactive polonium and radium later used to treat cancer.

The genetic effects of radiation, including the effects on cancer risk, were recognized much later. In 1927 Hermann Joseph Muller published research showing genetic effects, and in 1946 was awarded the Nobel prize for his findings.

More generally, the 1930s saw attempts to develop a general model for radiobiology. Notable here was Douglas Lea, [17] [18] whose presentation also included an exhaustive review of some 400 supporting publications. [19] [20]

Before the biological effects of radiation were known, many physicians and corporations had begun marketing radioactive substances as patent medicine and radioactive quackery. Examples were radium enema treatments, and radium-containing waters to be drunk as tonics. Marie Curie spoke out against this sort of treatment, warning that the effects of radiation on the human body were not well understood. Curie later died of aplastic anemia caused by radiation poisoning. Eben Byers, a famous American socialite, died of multiple cancers (but not acute radiation syndrome) in 1932 after consuming large quantities of radium over several years; his death drew public attention to dangers of radiation. By the 1930s, after a number of cases of bone necrosis and death in enthusiasts, radium-containing medical products had nearly vanished from the market.

In the United States, the experience of the so-called Radium Girls, where thousands of radium-dial painters contracted oral cancers [21] (but no cases of acute radiation syndrome [22] ), popularized the warnings of occupational health associated with radiation hazards. Robley D. Evans, at MIT, developed the first standard for permissible body burden of radium, a key step in the establishment of nuclear medicine as a field of study. With the development of nuclear reactors and nuclear weapons in the 1940s, heightened scientific attention was given to the study of all manner of radiation effects.

The atomic bombings of Hiroshima and Nagasaki resulted in a large number of incidents of radiation poisoning, allowing for greater insight into its symptoms and dangers. Red Cross Hospital surgeon Dr. Terufumi Sasaki led intensive research into the Syndrome in the weeks and months following the Hiroshima bombings. Dr Sasaki and his team were able to monitor the effects of radiation in patients of varying proximities to the blast itself, leading to the establishment of three recorded stages of the syndrome. Within 25–30 days of the explosion, the Red Cross surgeon noticed a sharp drop in white blood cell count and established this drop, along with symptoms of fever, as prognostic standards for Acute Radiation Syndrome. [23] Actress Midori Naka, who was present during the atomic bombing of Hiroshima, was the first incident of radiation poisoning to be extensively studied. Her death on August 24, 1945 was the first death ever to be officially certified as a result of radiation poisoning (or "Atomic bomb disease").

Areas of interest

The interactions between organisms and electromagnetic fields (EMF) and ionizing radiation can be studied in a number of ways:

The activity of biological and astronomical systems inevitably generates magnetic and electrical fields, which can be measured with sensitive instruments and which have at times been suggested as a basis for "esoteric" ideas of energy.

Radiation sources for experimental radiobiology

Radiobiology experiments typically make use of a radiation source which could be:

See also

Related Research Articles

Background radiation is a measure of the level of ionizing radiation present in the environment at a particular location which is not due to deliberate introduction of radiation sources.

Acute radiation syndrome Health problems caused by exposure to very high levels of ionizing radiation

Acute radiation syndrome (ARS), also known as radiation sickness, is a collection of health effects due to exposure to high amounts of ionizing radiation over a short period of time. Within the first days symptoms may include nausea, vomiting, and loss of appetite. This may then be followed by a few hours or weeks with little symptoms. After this, depending on the total dose of radiation, people may develop infections, bleeding, dehydration, and confusion, or there may be a period with few symptoms. This is finally followed by either recovery or death. The symptoms can begin within one hour and may last for several months.

The gray is a derived unit of ionizing radiation dose in the International System of Units (SI). It is defined as the absorption of one joule of radiation energy per kilogram of matter.

Radiation dosimetry in the fields of health physics and radiation protection is the measurement, calculation and assessment of the ionizing radiation dose absorbed by an object, usually the human body. This applies both internally, due to ingested or inhaled radioactive substances, or externally due to irradiation by sources of radiation.

Radiation protection, also known as radiological protection, is defined by the International Atomic Energy Agency (IAEA) as "The protection of people from harmful effects of exposure to ionizing radiation, and the means for achieving this". Exposure can be from a source of radiation external to the human body or due to internal irradiation caused by the ingestion of radioactive contamination.

Equivalent dose is a dose quantity H representing the stochastic health effects of low levels of ionizing radiation on the human body which represents the probability of radiation-induced cancer and genetic damage. It is derived from the physical quantity absorbed dose, but also takes into account the biological effectiveness of the radiation, which is dependent on the radiation type and energy. In the SI system of units, the unit of measure is the sievert (Sv).

The roentgen equivalent man is an older, CGS unit of equivalent dose, effective dose, and committed dose which are measures of the health effect of low levels of ionizing radiation on the human body.

Absorbed dose is a dose quantity which is the measure of the energy deposited in matter by ionizing radiation per unit mass. Absorbed dose is used in the calculation of dose uptake in living tissue in both radiation protection, and radiology. It is also used to directly compare the effect of radiation on inanimate matter such as in radiation hardening.

The International Commission on Radiological Protection (ICRP) is an independent, international, non-governmental organization, with the mission to provide recommendations and guidance on radiological protection concerning ionising radiation.

In radiobiology, the relative biological effectiveness is the ratio of biological effectiveness of one type of ionizing radiation relative to another, given the same amount of absorbed energy. The RBE is an empirical value that varies depending on the particles, energies involved, and which biological effects are deemed relevant.

The collective effective dose, dose quantity S, is calculated as the sum of all individual effective doses over the time period or during the operation being considered due to ionizing radiation. It can be used to estimate the total health effects of a process or accidental release involving ionizing radiation to an exposed population. The total collective dose is the dose to the exposed human population between the time of release until its elimination from the environment, perhaps integrating to time equals infinity. However, doses are generally reported for specific populations and a stated time interval. The International Commission on Radiological Protection (ICRP) states:"To avoid aggregation of low individual doses over extended time periods and wide geographical regions the range in effective dose and the time period should be limited and specified.

Gamma ray Energetic electromagnetic radiation arising from radioactive decay of atomic nuclei

A gamma ray, or gamma radiation, is a penetrating electromagnetic radiation arising from the radioactive decay of atomic nuclei. It consists of the shortest wavelength electromagnetic waves and so imparts the highest photon energy. Paul Villard, a French chemist and physicist, discovered gamma radiation in 1900 while studying radiation emitted by radium. In 1903, Ernest Rutherford named this radiation gamma rays based on their relatively strong penetration of matter; he had previously discovered two less penetrating types of decay radiation, which he named alpha rays and beta rays in ascending order of penetrating power.

Effective dose is a dose quantity in the International Commission on Radiological Protection (ICRP) system of radiological protection.

The Columbia University Center for Radiological Research (CRR) was founded more than 75 years ago to better understand the human health risks associated with exposure to ionizing radiation exposure. It is the oldest and largest such research center in the world. The Center's efforts are focused on unraveling the biological and molecular mechanisms underlying radiation effects in cells, tissues, organ systems and living organisms and how radiation exposure affects human health. Its primary mission is to provide an unbiased, comprehensive and independent source of scientific information about radiation risks to governmental agencies, elected officials, non-profit institutions and private entities to enable them to make sound, evidence based policy decisions. The CRR also provides basic science training to the next generation of radiobiologists, medical and health physicists and clinical radiologists. The Center's multidisciplinary staff encompasses professionals from diverse fields including molecular biology, cell biology, radiation physics, computational physics, engineering, radiation oncology and public health.

The committed dose in radiological protection is a measure of the stochastic health risk due to an intake of radioactive material into the human body. Stochastic in this context is defined as the probability of cancer induction and genetic damage, due to low levels of radiation. The SI unit of measure is the sievert.

Gioacchino Failla American scientist

Gioacchino Failla was an Italian-born American physicist. A pioneer in both biophysics and radiobiology, he was particularly noted for his work on the role of radiation as a cause of cancer and genetic mutation. He was born in Castelbuono in the Province of Palermo and emigrated with his family to the United States in 1906. After his retirement from Columbia University's Center for Radiological Research in 1960, he was appointed Senior Scientist Emeritus in the Radiological Physics Division of the Argonne National Laboratory in Illinois. He was killed in a car accident near the laboratory at the age of 70.

References

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Further reading