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الكلية كلية العلوم     القسم قسم علوم الحياة     المرحلة 3
أستاذ المادة اياد محمد جبر المعموري       10/26/2011 11:14:43 PM
Lecture- 2-

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:
Activity in Becquerel 1-1
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

1-4Organization of Cells and Tissues

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). All the compartments are separated by membranes, which allow concentration gradients of certain types of ions or molecules to remain. This is also true for the outer cell membrane, separating the inner cell volume from the environment.

A typical characteristic of many cells is their ability to grow and to produce two identical daughter cells by cell division. This division requires the exact duplication of the DNA contained in the cell nucleus, and the precise distribution of each of the two copies into the daughter cells. In general, proliferating cells in tissue as well as under laboratory conditions show a very regular division cycle, Beginning with a cell that was just produced by division of a predecessor, it starts with a preparation phase, which is necessary to initiate the DNA replication (G1-phase).
It is followed by the replication or synthesis of DNA (S-phase), and before cell division takes place a second preparation phase (G2-phase) is required. During the short interval of mitosis (M-phase), the DNA is packed in an extremely condensed form, microscopically visible as chromosomes, which are then symmetrically distributed to the two daughter cells. The total time for a complete division cycle of typical mammalian cells under laboratory conditions is in the order of 12–24 h.
The progress through the cell cycle and the DNA synthesis are highly organized and controlled processes Proliferation, e.g., depends on the environmental conditions and the integrity of the DNA molecule. Under certain circumstances, cells can leave the regular cycle and stay in a resting phase (G0-phase), but upon appropriate stimuli are still able to reenter the normal cycle.
The compartmentalization of tissues is maintained by a complex network of
signaling and interaction between the different cells and cell types. Signaling between cells can be achieved in principally two different ways:
1-- By exchange of small signaling molecules through particular channels (‘gap junctions’) connecting neighboring cells; this type of interaction requires direct cell-cell contacts
2- By diffusion-controlled exchange of molecules through the intercellular space, which are recognized by the target cells through receptors on the outer cell membrane.

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.

*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.

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