Radiobiology – Radiation Biology

Radiation biology (also known as radiobiology) is a medical science that involves the study of biological effects of ionizing radiation on living tissues. Radiation is all around us. In, around, and above the world we live in. It is a natural energy force that surrounds us. It is a part of our natural world that has been here since the birth of our planet. Whether the source of radiation is natural or man-made, whether it is a large dose of radiation or a small dose, there will be some biological effects. In general, ionizing radiation is harmful and potentially lethal to living beings but can have health benefits in medicine, for example, in radiation therapy for the treatment of cancer and thyrotoxicosis. This chapter briefly summarizes the short and long term consequences which may result from exposure to radiation.

Cellular Damage – Radiobiology

All biological damage effects begin with the consequence of radiation interactions with the atoms forming the cells. All living things are composed of one or more cells. Every part of your body consists of cells or was built by them. Although we tend to think of biological effects in terms of the effect of radiation on living cells, in actuality, ionizing radiation, by definition, interacts only with atoms by a process called ionization. For ionizing radiation, the kinetic energy of particles (photons, electrons, etc.) of ionizing radiation is sufficient and the particle can ionize (to form ion by losing electrons) target atoms to form ions. Simply ionizing radiation can knock electrons from an atom.

There are two mechanisms by which radiation ultimately affects cells. These two mechanisms are commonly called:

  • Direct effects. Direct effects are caused by radiation, when radiation interacts directly with the atoms of the DNA molecule, or some other cellular component critical to the survival of the cell. The probability of the radiation interacting with the DNA molecule is very small since these critical components make up such a small part of the cell.
  • Indirect effects. Indirect effects are caused by interaction of radiation usually with water molecules. Each cell, just as is the case for the human body, is mostly water. Ionizing radiation may break the bonds that hold the water molecule together, producing radicals such as hydroxyl OH, superoxide anion O2and others. These radicals can contribute to the destruction of the cell.

A large number of cells of any particular type is called a tissue. If this tissue forms a specialised functional unit, it is called an organ. The type and number of cells affected is also an important factor. Some cells and organs in the body are more sensitive to ionizing radiation than others.

Sensitivity of various types of cells to ionizing radiation is very high for tissues consisting of cells that divide rapidly like those found in bone marrow, stomach, intestines, male and female reproductive organs, and developing fetuses.  This is because dividing cells require correct DNA information in order for the cell’s offspring to survive. A direct interaction of radiation with an active cell could result in the death or mutation of the cell, whereas a direct interaction with the DNA of a dormant cell would have less of an effect.

As a result, living cells can be classified according to their rate of reproduction, which also indicates their relative sensitivity to radiation. As a result, actively reproducing cells are more sensitive to ionizing radiation than cells that make up skin, kidney or liver tissue. The nerve and muscle cells are the slowest to regenerate and are the least sensitive cells.

tissue weighting factor - ICRPThe sensitivity of the various organs of the human body correlate with the relative sensitivity of the cells from which they are composed. In practice, this sensitivity is represented by the tissue weighting factorwT, which is the factor by which the equivalent dose in a tissue or organ T is weighted to represent the relative contribution of that tissue or organ to the total health detriment resulting from uniform irradiation of the body (ICRP 1991b).

If a person is irradiated only partially, the dose will depend strongly on the tissue, which was irradiated. For example, a 10 mSv gamma dose to the whole body and a 50 mSv dose to the thyroid is the same, in terms of risk, as a whole-body dose of 10 + 0.04 x 50 = 12 mSv.

High-LET and Low-LET Radiation

Radiation weighting factors - current - ICRP
Source: ICRP Publ. 103: The 2007 Recommendations of the International Commission on Radiological Protection

As was written, each type of radiation interacts with matter in a different way. For example charged particles with high energies can directly ionize atoms. Alpha particles are fairly massive and carry a double positive charge, so they tend to travel only a short distance and do not penetrate very far into tissue if at all. However alpha particles will deposit their energy over a smaller volume (possibly only a few cells if they enter a body) and cause more damage to those few cells.

Beta particles (electrons) are much smaller than alpha particles. They carry a single negative charge. They are more penetrating than alpha particles. They can travel several meters but deposit less energy at any one point along their paths than alpha particles. This means beta particles tend to damage more cells, but with lesser damage to each. On the other hand electrically neutral particles interacts only indirectly, but can also transfer some or all of their energies to the matter.

It would certainly simplify matters if biological effects of radiation were directly proportional to the absorbed dose. Unfortunately, biological effects depend also on the way in which the absorbed dose is distributed along the path of the radiation. Studies have shown that alpha and neutron radiation cause greater biological damage for a given energy deposition per kg of tissue than gamma radiation does. It was discovered, biological effects of any radiation increases with the linear energy transfer (LET). In short, the biological damage from high-LET radiation (alpha particlesprotons or neutrons) is much greater than that from low-LET radiation (gamma rays). This is because the living tissue can more easily repair damage from radiation that is spread over a large area than that which is concentrated in a small area. Of course, at very high levels of exposure gamma rays can still cause a great deal of damage to tissues.

Because more biological damage is caused for the same physical dose (i.e., the same energy deposited per unit mass of tissue), one gray of alpha or neutron radiation is more harmful than one gray of gamma radiation. This fact that radiations of different types (and energies) give different biological effects for the same absorbed dose is described in terms of factors known as the relative biological effectiveness (RBE) and the radiation weighting factor (wR).

Acute Dose and Chronic Dose

Biological effects of radiation and their consequences depends strongly on the level of dose rate obtained. In radiobiology, the dose rate is a measure of radiation dose intensity (or strength). Low-level doses are common for everyday life. In the following points there are a few examples of radiation exposure, which can be obtained from various sources.

  • 05 µSv – Sleeping next to someone
  • 09 µSv – Living within 30 miles of a nuclear power plant for a year
  • 1 µSv – Eating one banana
  • 3 µSv – Living within 50 miles of a coal power plant for a year
  • 10 µSv – Average daily dose received from natural background
  • 20 µSv – Chest X-ray

From biological consequences point of view, it is very important to distinguish between doses received over short and extended periods.  Therefore, biological effects of radiation are typically divided into two categories.

  • Acute Doses. An “acute dose” (short-term high-level dose) is one that occurs over a short and finite period of time, i.e., within a day.
  • Chronic Doses. A “chronic dose” (long-term low-level dose) is a dose that continues for an extended period of time, i.e., weeks and months, so that it is better described by a dose rate.

High doses tend to kill cells, while low doses tend to damage or change them. High doses can cause visually dramatic radiation burns, and/or rapid fatality through acute radiation syndrome. Acute doses below 250 mGy are unlikely to have any observable effects. Acute doses of about 3 to 5 Gy have a 50% chance of killing a person some weeks after the exposure, if a person receives no medical treatment.

Low doses spread out over long periods of time don’t cause an immediate problem to any body organ. The effects of low doses of radiation occur at the level of the cell, and the results may not be observed for many years. Moreover, some studies demonstrate, most of human tissues exhibit a more pronounced tolerance to the effects of low-LET radiation in case of a prolonged exposure compared to a one-time exposure to a similar dose.

Deterministic and Stochastic Effects

In radiobiology, most adverse health effects of radiation exposure are usually divided into two broad classes:

  • Deterministic effects are threshold health effects, that are related directly to the absorbed radiation dose and the severity of the effect increases as the dose increases.
  • Stochastic effects occur by chance, generally occurring without a threshold level of dose. Probability of occurrence of stochastic effects is proportional to the dose but the severity of the effect is independent of the dose received.

Deterministic Effects

In radiobiology, deterministic effects (or non-stochastic health effects) are health effects, that are related directly to the absorbed radiation dose and the severity of the effect increases as the dose increases. Deterministic effects have a threshold below which no detectable clinical effects do occur. The threshold may be very low (of the order of magnitude of 0.1 Gy or higher) and may vary from person to person. For doses between 0.25 Gy and 0.5 Gy slight blood changes may be detected by medical evaluations and for doses between 0.5 Gy and 1.5 Gy blood changes will be noted and symptoms of nausea, fatigue, vomiting occur.

Once the threshold has been exceeded, the severity of an effect increases with dose. The reason for the presence of this threshold dose is that radiation damage (serious malfunction or death) of a critical population of cells (high doses tend to kill cells) in a given tissue needs to be sustained before injury is expressed in a clinically relevant form. Therefore, deterministic effects are also termed tissue reaction. They are also called non-stochastic effects to contrast with chance-like stochastic effects (e.g. cancer induction).

Deterministic effects are not necessarily more or less serious than stochastic effects. High doses can cause visually dramatic radiation burns, and/or rapid fatality through acute radiation syndrome. Acute doses below 250 mGy are unlikely to have any observable effects. Acute doses of about 3 to 5 Gy have a 50% chance of killing a person some weeks after the exposure, if a person receives no medical treatment. Deterministic effects can ultimately lead to a temporary nuisance or also to a fatality. Examples of deterministic effects:

Examples of deterministic effects are:

  • Acute radiation syndrome, by acute whole-body radiation
  • Radiation burns, from radiation to a particular body surface
  • Radiation-induced thyroiditis, a potential side effect from radiation treatment against hyperthyroidism
  • Chronic radiation syndrome, from long-term radiation.
  • Radiation-induced lung injury, from for example radiation therapy to the lungs

Lethal Doses of Radiation

The lethal dose of radiation (LD) is an indication of the lethal amount radiation. In radiation protection, the median lethal dose, LDXY is usually used. For example, the dose of radiation expected to cause death to 50 % of the irradiated persons within 30 days is LD50/30.  LD1 is the dose expected to cause death to 1% of the irradiated persons, consequently, LD99 is lethal for all (99%) persons irradiated. It is also very important, whether a person receives some medical treatment or not. The greater an acute radiation dose is, the greater is the possibility of it killing the individual. For a healthy adult, the LD50 is estimated to be somewhere between 3 and 5 Gy.

  • 2.5 Sv – Dose that kills a human with a 1% risk (LD1), if the dose is received over a very short duration.
  • 5 Sv – Dose that kills a human with a 50% risk within 30 days (LD50/30), if the dose is received over a very short duration. Cause of death will be loss of bone marrow function.
  • 8 Sv – Dose that kills a human with a 99% risk (LD99), if the dose is received over a very short duration. At around 10 Gy, acute inflammation of the lungs can occur and lead to death.

The lethal dose data given above apply to acute gamma doses delivered in a very short time, e.g., a few minutes. More dose is required to produce the effects listed above, if the dose is received over a period of hours or longer.

Stochastic Effects

In radiobiology, stochastic effects of ionizing radiation occur by chance, generally occurring without a threshold level of dose. Probability of occurrence of stochastic effects is proportional to the dose but the severity of the effect is independent of the dose received. The biological effects of radiation on people can be grouped into somatic and hereditary effects. Somatic effects are those suffered by the exposed person. Hereditary effects are those suffered by the offspring of the individual exposed. Cancer risk is usually mentioned as the main stochastic effect of ionizing radiation, but also hereditary disorders are stochastic effects.

According to ICRP:

(83) On the basis of these calculations the Commission proposes nominal probability coefficients for detriment-adjusted cancer risk as 5.5 x 10-2 Sv-1 for the whole population and 4.1 x 10-2 Sv-1 for adult workers. For heritable effects, the detriment-adjusted nominal risk in the whole population is estimated as 0.2 x 10-2 Sv-1 and in adult workers as 0.1 x 10-2 Sv-1 .

Special Reference: ICRP, 2007. The 2007 Recommendations of the International Commission on Radiological Protection. ICRP Publication 103. Ann. ICRP 37 (2-4).

The SI unit for effective dose, the sievert, represents the equivalent biological effect of the deposit of a joule of gamma rays energy in a kilogram of human tissue. As a result, one sievert represents a 5.5% chance of developing cancer. Note that, the effective dose is not intended as a measure of deterministic health effects, which is the severity of acute tissue damage that is certain to happen, that is measured by the quantity absorbed dose.

There are three general categories of stochastic effects resulting from exposure to low doses of radiation. These are:

  • Genetic effects. The genetic effect is suffered by the offspring of the individual exposed. It involves the mutation of very specific cells, namely the sperm or egg cells. Radiation is an example of a physical mutagenic agent. Note that, there are also many chemical agents as well as biological agents (such as viruses) that cause mutations. One very important fact to remember is that radiation increases the spontaneous mutation rate, but does not produce any new mutations.
  • Somatic effects. Somatic effects are those suffered by the exposed person. The most common impact of irradiation is the stochastic induction of cancer with a latent period of years or decades after exposure. Since cancer is the primary result, it is sometimes called the carcinogenic effect. Radiation is an example of a physical carcinogenic, while cigarettes are an example of a chemical cancer causing agent. Viruses are examples of biological carcinogenic agents.
  • In-Utero effects involve the production of malformations in developing embryos. However, this is actually a special case of the somatic effect, since the embryo/fetus is the one exposed to the radiation.

Somatic effects as a result of exposure to radiation are thought by most to occur in a stochastic manner. 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. This model is known as the linear no-threshold model (LNT). This model assumes, that there is no threshold point and risk increases linearly with a dose. 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. The LNT is not universally accepted with some proposing an adaptive dose–response relationship where low doses are protective and high doses are detrimental. It must be emphasized, that a number of organisations disagree with using the linear no-threshold model to estimate risk from environmental and occupational low-level radiation exposure.

Radiobiology and Dose Limits

In radiation protection, dose limits are set to limit stochastic effects to an acceptable level, and to prevent deterministic effects completely. Note that, stochastic effects are those arising from chance: the greater the dose, the more likely the effect. Deterministic effects are those which normally have a threshold: above this, the severity of the effect increases with the dose. Dose limits are a fundamental component of radiation protection, and breaching these limits is against radiation regulation in most countries. Note that, the dose limits described in this article apply to routine operations. They do not apply to an emergency situation when human life is endangered. They do not apply in emergency exposure situations where an individual is attempting to prevent a catastrophic situation.

The limits are split into two groups, the public, and occupationally exposed workers. According to ICRP, occupational exposure refers to all exposure incurred by workers in the course of their work, with the exception of

  1. excluded exposures and exposures from exempt activities involving radiation or exempt sources
  2. any medical exposure
  3. the normal local natural background radiation.

The following table summarizes dose limits for occupationally exposed workers and for the public:

dose limits - radiation
Table of dose limits for occupationally exposed workers and for the public.
Source of data: ICRP, 2007. The 2007 Recommendations of the International Commission on Radiological Protection. ICRP Publication 103. Ann. ICRP 37 (2-4).

According to the recommendation of the ICRP in its statement on tissue reactions of 21. April 2011, the equivalent dose limit for the lens of the eye for occupational exposure in planned exposure situations was reduced from 150 mSv/year to 20 mSv/year, averaged over defined periods of 5 years, with no annual dose in a single year exceeding 50 mSv.

Limits on effective dose are for the sum of the relevant effective doses from external exposure in the specified time period and the committed effective dose from intakes of radionuclides in the same period. For adults, the committed effective dose is computed for a 50-year period after intake, whereas for children it is computed for the period up to age 70 years. The effective whole-body dose limit of 20 mSv is an average value over five years. The real limit is 100 mSv in 5 years, with not more than 50 mSv in any one year.

References:

Radiation Protection:

  1. Knoll, Glenn F., Radiation Detection and Measurement 4th Edition, Wiley, 8/2010. ISBN-13: 978-0470131480.
  2. Stabin, Michael G., Radiation Protection and Dosimetry: An Introduction to Health Physics, Springer, 10/2010. ISBN-13: 978-1441923912.
  3. Martin, James E., Physics for Radiation Protection 3rd Edition, Wiley-VCH, 4/2013. ISBN-13: 978-3527411764.
  4. U.S.NRC, NUCLEAR REACTOR CONCEPTS
  5. U.S. Department of Energy, Nuclear Physics and Reactor Theory. DOE Fundamentals Handbook, Volume 1 and 2. January 1993.

Nuclear and Reactor Physics:

  1. J. R. Lamarsh, Introduction to Nuclear Reactor Theory, 2nd ed., Addison-Wesley, Reading, MA (1983).
  2. J. R. Lamarsh, A. J. Baratta, Introduction to Nuclear Engineering, 3d ed., Prentice-Hall, 2001, ISBN: 0-201-82498-1.
  3. W. M. Stacey, Nuclear Reactor Physics, John Wiley & Sons, 2001, ISBN: 0- 471-39127-1.
  4. Glasstone, Sesonske. Nuclear Reactor Engineering: Reactor Systems Engineering, Springer; 4th edition, 1994, ISBN: 978-0412985317
  5. W.S.C. Williams. Nuclear and Particle Physics. Clarendon Press; 1 edition, 1991, ISBN: 978-0198520467
  6. G.R.Keepin. Physics of Nuclear Kinetics. Addison-Wesley Pub. Co; 1st edition, 1965
  7. Robert Reed Burn, Introduction to Nuclear Reactor Operation, 1988.
  8. U.S. Department of Energy, Nuclear Physics and Reactor Theory. DOE Fundamentals Handbook, Volume 1 and 2. January 1993.
  9. Paul Reuss, Neutron Physics. EDP Sciences, 2008. ISBN: 978-2759800414.

See above:

Radiation Protection