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الكلية كلية العلوم     القسم قسم علوم الحياة     المرحلة 3
أستاذ المادة اياد محمد جبر المعموري       03/12/2016 17:42:58
Lecture- 3-

1-General Aspects of Radiation Damage to Cells and Tissues.
Before we know the radiation damage , we must explain some important factors participate in this damage:
1-1 Activity in Becquerel
When an atom disintegrates, radiation is emitted. If the rate of disintegrations is large, a radioactive source is considered to have a high activity.
The unit for the activity of a radioactive source was named after Becquerel
(abbreviated Bq) and is defined as:

1 Bq = 1 disintegration per sec.

In a number of countries, the old unit, the curie (abbreviated Ci and named after Marie Curie) is still used. The curie-unit was defined as the activity in one gram of radium. The number of disintegrations per second in one gram of radium is 37 billion. The relation between the curie and the becquerel is given by :
1 Ci = 3.7 . 1010 Bq
The accepted practice is to give the activity of a radioactive source in becquerel. This is because Bq is the unit chosen for the system of international units (SI units). But one problem is that the numbers in becquerel are always very large. The opposite holds true when a source is given in curies. For example, when talking about radioactivity in food products, 3,700 Bq per kilogram of meat is a large number. The same activity given in Ci is a really small number, 0.0000001 curie per kilogram.

1-2 Specific Activity
Specific activity is the activity per mass or volume unit. For example, the radioactivity in meat is given as Bq/kg. For liquids the specific activity is given in Bq/l and for air and gases the activity is given as Bq/m3.
In the case of fallout from a nuclear test or accident, the activity on surfaces can be given either as Bq/m2 or as Ci/km2. Both are used to describe radioactive pollution. The conversion between them is:
1 Ci/km2 = 37,000 Bq/m2
A great deal of information must be considered to calculate radiation doses and risk factors associated with these specific activities. The information must include the specific activity along with the various types of isotopes, their energies, physical and biological half-lives and methods of entry into the body. After considering all of these factors and calculating the dose, a determination of medical risk can be calculated.

The Figure below indicates how the distribution of absorbed energy in a system (for example an animal cell) might look after different types of radiation have passed through. The upper circle (field of view) contains tracks produced by x- and ?-ray absorption and the lower circle contains the track of an ?-particle. Each dot represents an ionized molecule. The number of dots within the two circles is the same, indicating the same radiation dose. However, note that the distribution of dots (ionizations) is quite different. The top is an example of low LET (linear energy transfer) and the bottom is an example of high LET

Linear energy transfer (LET) is a term used in dosimetry. It describes the action of radiation upon matter. It is identical to the retarding force acting on a charged ionizing particle travelling through the matter.[1] It describes how much energy an ionizing particle transfers to the material traversed per unit distance. By definition, LET is a positive quantity. LET depends on the nature of the radiation as well as on the material traversed.

This is a type of ionizing radiation that deposit a large amount of energy in a small distance.
Neutrons , alpha particles
This is a type of ionizing radiation that deposit less amount of energy along the track or have infrequent or widely spaced ionizing events.
x-rays, gamma rays
1-4 Organization of Cells and Tissues

The following are possible effects of radiation on cells:
1-Cells are undamaged by the dose
Ionization may form chemically active substances which in some cases alter the structure of the cells. These alterations may be the same as those changes that occur naturally in the cell and may have no negative effect.
2-Cells are damaged, fix the damage and continue working normally
Some ionizing events produce substances not normally found in the cell. These can lead to a breakdown of the cell structure and its components. Cells can repair the damage if it is limited. Even damage to the chromosomes is usually repaired. Many thousands of chromosome aberrations (changes) occur constantly in our bodies. We have effective mechanisms to repair these changes.
3-Cells are damaged, overcome the damage and work abnormally
If a damaged cell needs to perform a function before it has had time to repair itself, it will either be unable to perform the repair function or perform the function incorrectly or incompletely. The result may be cells that cannot perform their normal functions or that now are damaging to other cells. These altered cells may be unable to reproduce themselves or may reproduce at an uncontrolled rate. Such cells can be the underlying causes of cancers.
4-Cells die due to the damage
If a cell is extensively damaged by radiation, or damaged in such a way that reproduction is affected, the cell may die. Radiation damage to cells may depend on how sensitive the cells are to radiation.

A single cell represents the smallest functional unit of any complex organized tissue. In general, within a single cell two clearly separated compartments can be distinguished visually and functionally: the cell nucleus and the cytoplasm. The cell nucleus contains the genetic information in the form of a large macromolecule, the DNA. In combination with additional proteins, secondary, tertiary, and higher order structures are built, resulting in a condensed structure of the DNA molecule. Within the cytoplasm, further substructures (organelles) can be distinguished. These comprise, e.g., the mitochondria (responsible for the energy production), the endoplasmic reticulum in combination with the ribosomes (which are involved in the assembly of proteins), and the Golgi apparatus (involved in further processing and transport of macromolecules within the cell and out of the cell).

Figure 1: Cell damage by Radiation
1-5 Cellular Effects of Radiation
Starting from the structural complexity of a single cell, the question arises which compartment is most sensitive to radiation and can thus be expected to be responsible for the observable response of a cell to radiation? Experimental results using viruses, bacteria, yeast, and mammalian cells have demonstrated a correlation between the radio sensitivity and the DNA content, at least for groups of biologically similar objects: the higher the amount of DNA, the more sensitive the object (overview in These results already suggested that DNA plays a key role in the response to radiation. This hypothesis has been proven also more directly for mammalian cells. The experiments revealed that energy deposition in the nucleus is by far more efficient to produce biological damage, compared to the case where similar amounts of energy are deposited to the cytoplasm only. Cells were shown to respond to energy deposits in the nucleus at a level approximately 100 times lower than that required to detect similar biological effects, when only the cytoplasm is irradiated. Several other experiments also support the view that the DNA molecule represents the critical target for radiation effects in cells. However, there is increasing evidence in the last few years that DNA damage is not necessarily a prerequisite for the induction of biologically relevant effects.

Figure 2: Cellular Effects of Radiation on DNA
*Radiation induced DNA damage. For clarity, the DNA double helix is drawn as a flat, ladder-like structure. This figure summarizes the major types of DNA damage induced by ionizing radiation, whether by the direct or by the indirect effect. It has to be taken into account, however, that these types of lesions do not necessarily occur separately, but instead, depending on the dose level, combinations of different types occurring in close vicinity can lead to more complex lesions. Since the information on both strands of the DNA molecule is complementary, all injuries affecting only one side of the DNA double strand can potentially be easily repaired by using the information on the intact strand as a template.
DNA damage can be induced by radiation in two different ways. On the one hand, radiation leads to ionizing events in the DNA molecule itself subsequently leading to breakage of molecular bonds and disruption of one or both strands of the DNA. These events are termed ‘direct effect’. On the other hand, radiation leads to the production of, e.g., highly reactive OH-radicals by radiolysis of the water molecules surrounding the DNA molecule. These radicals are able to migrate over distances of a few nanometers during their lifetime and are thus capable of damaging the DNA molecule, even if produced at a certain distance. This action is termed ‘indirect effect higher organisms like, e.g., mammalian cells are in general able to recognize and to repair damage to DNA at least to a certain extent
The efficiency of these repair processes depends on the complexity of the damage induced. For example, single strand breaks can be repaired comparatively easily, because this type of lesion resembles naturally occurring events during the replication cycle, e.g., when the double strand has to be opened on one strand to allow the access of replication proteins to the DNA. The protein machinery of the cell is well prepared to handle these events. With increasing complexity, however, damage becomes more difficult to repair, and this might enhance the probability that the repair process cannot be accomplished correctly, leaving a partially repaired or modified DNA molecule the investigation of cellular repair pathways is an important field of current biological research, and these processes are by far not yet fully understood. Most studies have been performed using relatively simple biological objects like, bacteria and yeast cells, but for the greatest part of pathways it could be shown that analogous mechanisms exist also in more complex organisms like, e.g., mammalian cells.

1-6 Cellular Sensitivity to Radiation

Not all living cells are equally sensitive to radiation. Those cells which are actively reproducing are more sensitive than those which are not, since dividing cells require that the DNA information be correct in order for the cell s offspring to survive. A direct interaction of radiation could result in the death or mutation of such a cell, whereas a direct interaction with the DNA of a dormant cell would have less of an effect.
As consequences, living cells can be classified according to their rate of reproduction, which also indicates their relative sensitivity to radiation. This means that different cell systems have different sensitivities.
A-Lymphocytes (white blood cells) and cells which produce blood are constantly regenerating, and are therefore the most sensitive.
B-Reproductive and gastrointestinal cells do not regenerate as quickly and are less sensitive.
C-Nerve and muscle cells are the slowest to regenerate and are the least sensitive.
Cells, like the human body, have a tremendous ability to repair damage. As a result, not all radiation effects are irreversible. In many instances, the cells are able to completely repair any damage and function normally.
In some cases, however, the damage is severe enough that the cell dies. In other instances, the cell is damaged but is still able to reproduce. The daughter cells, however, may be lacking some critical life-sustaining component, and they die. Finally, the cell may be affected in such a way that it does not die but is simply mutated. The mutated cell reproduces and thus perpetuates the mutation. This could be the beginning of a malignant tumor.

References

COURT-BROWN, W.M., DOLL, R., “Leukaemia and aplastic anaemia in patients irradiated for ankylosing spondylitis” 1957, J. Radiol. Prot. (2007), 27 (4B) B15-B154.

INTERNATIONAL COMMISSION ON RADIOLOGICAL PROTECTION: Biological effects after prenatal irradiation (embryo and foetus), ICRP publication 90, Ann. ICRP 33
(2003).

INTERNATIONAL COMMISSION ON RADIOLOGICAL PROTECTION: Low dose extrapolation of radiation-related cancer risk, ICRP publication 99, Ann. ICRP 35(4) (2006).

PRESTON, D.L., RON, E., TOKUOKA, S., et al., “Solid cancer incidence in atomic bomb survivors 1958-1998”, Radiat. Res, (2007), 168 1-64.

SANKARANARAYANAN, K., “Estimation of the genetic risks of exposure to ionizing radiation in humans: current status and emerging perspectives”, J. Radiat. Res. (2006), 47, suppl. B57-B66.

TROTT, K.R., KAMPRAD, F., “Estimation of cancer risks from radiotherapy of benign diseases”, Strahlenther Onkol. (2006), 182, 431-436.

TUBIANA, M., AURENGO, A., AVERBECK, D. et al., Dose-effect relationships and estimation of the carcinogenic effects of low doses of ionising radiation, Académie des Sciences – Académie Nationale de Médecine, Paris (2005).

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