CHAPTER 2 Interaction of Radiation with Matter

Absorption -certain number of photons in the beam -interception of photons Attenuation -reduction in the number of photons as they pass through the matter Gamma radiation -considered to be a monoenergetic radiation -it can omit with single energy Half value layer -the amount of absorber that reduces intensity to half the original value X-Radiation -radiation composed of x-ray X-ray -polyenergetic; emit ted with many energies -attenuation is equal to primary radiation minus the remnant beam Transmission -photons that pass through matter but do not interact *low energy interacts with entire atom *high energy interacts with the nucleus *the photon of middle energies usually interact with orbital electron. Thisinteraction is usually seen in diagnostic xray and nuclear medicine Scatter -photons that change direction lose energy and may continue to interact again and scatter or be absorbed K shell electrons -electron that are closest to the positively charged nucleus, possess the greatest force of attraction to the nucleus or binding energy * Inner shell electrons have a high binding energy they have a low energy level * The farther an electron is from the nucleus, the lower the binding energy and the higher the energy level

Five interactions of x-rays and gamma rays with matter 1. Photoelectric effect -all of the energy of the incoming photon is lost - also known as photoelectric effect with total absorption -emission, or ejection, of electrons from the surface of, generally, a metal in response to incident light 2 basic rules of photoelectric interaction 1. Photoelectric interaction are more likely to occur if the x-ray photons energy is greater than, but close to, the binding energy of the electron 2. Photoelectric interaction have a greater likelihood of occurrence when the electron is more tightly bound in its orbit *Specific ionization -number of ion pairs produced per unit of distance traveled *linear energy transfer -used to quantify the effects of ionizing radiation on biological specimens or electronic devices -rate of energy depend on the particles as it travels through matter -unit: keV/um *alpha and beta have high SI and LET *x-radiation and gamma have low LET and SI *Characteristic cascade -the shell by shell process *Secondary radiation -having same effect with the scatter radiation -each photon between two shells has different energy 2. Coherent scatter -Also called Thomson Scattering Occurs primarily with low-energy xrays of below 10keV -photons causes excitation rather than ionization of the target atom

-The electron is ejected, and the photon is scattered 3. Compton scatter -electron is ejected from its orbital position and the photon loses energy because of the interaction but continues to travel in a different direction -the amount of energy lost or retained depends on the initial photon energy and the angle of deflection -Angle of scatter can range from 0-180 degrees -photon has to overcome a nuclear binding energy of 7 to 15 keV -Nucleus undergoes excitation and emits nuclear fragment * incedent photon -incoming x-ray photon from theprimary beam *Backscatter -scatter deflected at 180 degree angle *Compton or recoil electron -electron that has been set into motion by a collision 4. Pair production -the incoming photon must have energy of 1.02meV -energy of the photon in transformed into tow particles according to Einsteins formula E = mc2 -two particles is produced: y Negatron-negative charge y Positron- positively charge; from by the antimetter 5. Photodisintegration -occurs about 10meV -Photon has to overcome a nuclear binding energy of 7 to 15keV -interaction between high energy photon and nucleus -nucleus undergoes excitation and emits a nuclear fragment (neutron, proton, alpha particles, cluster of fragment)

Interaction of particulate radiation with matter Alpha -monoenergetic radiation Beta and positron -polyenergetic radiation *alpha,beta,positron -lose energy by producing of ion pairs Two main types of interaction y Elastic interaction -there is no charge in the total energy of the interaction particles y Inelastic interaction -A collision between bodies in which the total kinetic energy of the bodies is not conserved. Bremsstrahlung -interaction between alpha and beta Radiological unit -unit to compare effects of all type of ionizing radiation on humans Determining Radiation Dose X-ray Exposure *dose -amount of radiation absorbed by the patient -can be determining by the attenuation, absorption, and production of scatter 5 methods to measure the dose of the patient from x-ray examination 1. Skin dose -measure of radiation received by a portion of the patients skin 2. Entrance skin exposure used by some government agencies to regulate diagnostic x-ray exposure it is determined using the technical factors and geometry of an exposure such as lumbar spine or chest 3. Depth dose -measures the percentage of skin dose found at a certain depth within a patient 4. Organ dose

-the dose received by a particular organ 5. Integral dose -refers to the total amount of energy absorbed by a specific mass of tissue -may be an organ, tissue or the entire patient

CHAPTER 3
RADIATION DETECTION AND DOSIMETRY Radiation Units International Commission on radiological Units and Measurements (ICRU): In 1962, redefined many of the concepts and quantities of radiation measurement, proposed some new special units, and defined other units more precisely.  Roentgen (R): is a unit of exposure of x- or gamma radiation based on the ionization that these radiations produce in air.  An exposure of one roentgen results in 2.584 -4 x 10 coulomb per kilogram of air.  Unit is not applicable to particulate radiation, such as alphas, betas, or neutrons.  Multiples of Roentgen commonly used 3 o Kiloroentgen (kR): thousand R (10 R) o Milliroentgen (mR): thousandth of -3 an R (10 )  Exposure rate is usually expressed as Roentgens per hour (R/hr), roentgens per min (R/min) etc.  Rad: is a unit of absorbed dose and expresses the energy absorbed per gram of material from any ionizing radiation.  One rad is 100 ergs absorbed per gram of any substance  The number of rads is approximately equal to the number of roentgens.  Is used for particulate as well as electromagnetic radiation  Absorbed dose in rads is usually determined indirectly, often from ionization measurements.  Rem: is a unit of dose equivalent which is numerically equal to the dose in rads multiplied by the quality factor.  It was proposed to make allowances since the same dose in rads from different types of radiation does not necessarily produce the same degree of biological effect.  Allowance for the difference in biological effectiveness is made by the quality factor 

which relates the effect of other radiations to that of gamma rays from cobalt-60. Relative Biological Effectiveness (RBE): is used instead of quality factor to express the relative effectiveness of various radiations in experimental radiobiology.  RBE values are usually experimentally derived values which pertain only to the system under study. Quality Factor (QF): is another name for a linear-energy-transfer dependent factor by which absorbed doses are to be multiplied to account for the varying effectiveness of different radiations  Used for the purposes of radiation protection  Unit similar to RBE Dose Distribution Factor (DF): is a factor expressing the modification of biological effect due to nonuniform distribution of internally deposited radionuclides.  Used in the calculation of REM when internally deposited radionuclides are considered. Curie (Ci): is a unit of radioactivity and indicates the rate at which the atoms of a radioactive substance are decaying.  Originally defined as the activity of one gram of radium 10  One curie is 3.7x10 disintegrations per second Smaller units of Activity Curie 7 Millicurie (mCi= 10 3.7x10 3 disintegration/sec ) microcurie (uCi= 3.7x104 10-6) disintegration/sec nanocurie (nCi=10- 3.7 disintegration/sec 9 ) -2 picocurie (pCi=10 3.7x10 12 disintegration/sec ) 6  1 uCi = 2.2 x 10 dpm (disintegration per minute) The specific activity of a radioactive substance can be defined as the number of curies per gram of the element present, where the weight includes both stable and radioactive isotopes of the element ACTIVITY AND

RELATIONSHIP BETWEEN ABSORBED DOSE

External Source: an external source of radiation is one that is not contained within the material being exposed.  Alpha and beta rays are not ordinarily used for external radiation because of their relatively short path lengths in air.  Gamma rays (have long path length) and xrays are usually suitable/ common source of external radiation

Inverse Square Law: the radiation intensity varies inversely as the square of the distance from the source  Used with gamma sources Internal Sources: source that is contained within a system  Radionuclides which emit alpha or beta rays are frequently used as internal emitters  Bec. of the short path lengths of these radiations in tissue, usually assumed that most of the energy has been absorbed within the specimen.  Effective half-life includes both physical and biological half-life  RADIATION DETECTION AND MEASUREMENT Ionizing Chambers: operate as a result of the ionization which is produced in them by the passage of charged particles.  Most common method of measuring radiation exposure is with an ionizing chamber  Can be designed in many sizes and shapes  Used to measure all types of radiation that produce ionization  Principle of an ionization chamber:  When radiation produces ionization in the space between the plates, each component of the ion pair is attracted to the plate of opposite sign  Electrons move to positive plate (anode)  Positive ions move to the negative plate (cathode)  Small current results in the system  The number of ions collected and the resultant current flow depend on the amount of ionization produced by the radiation and the potential between plates.  If no potential is applied to the electrodes, recombination of electrons and positive ions occurs, no ions are collected on the plates, and no current flows.  If a small potential is applied, some of the electrons and positive ions are attracted.  Electrons and ions which do not reach the electrode recombine to form neural atoms  As the potential difference of the electrode is increased, numbers of electrons and ions reaching the plates increases  At some potential, all of the electrons and ions reach the electrodes, no recombination takes place  Alpha particle lose their energy at a higher rate than do beta particles  The number of ion pairs produced between the plates by an alpha particle is greater than the number produced by beta particles or gamma photon  Ions collected is greatest for an alpha particle  Gas amplification: As the potential across the electrodes is further increased, there is an

 

   

increase in the number of ions collected as a result of the formation of secondary ion pairs. Proportional Region: region where the number of secondary ionizations and the number of collected ions is proportional to the number of primary ion pairs produced by the radiation. Amplification factor is the same for each type of radiation. Gas amplification reaches a limit with further increase in voltage. Beyond this limit, all radiations, regardless of the number of primary ionizations, will yield the same maximum number of ions collected Geiger Region: voltage range where it is not possible to distinguish between types of radiation. Ions are collected on the electrodes in bursts or pulses In an Integrating circuit, pulses are smoothed out, and the recording instrument will measure the average voltage change or current flow through the system Pulse-type circuits: each pulse is registered separately, and the total number of pulse is recorded Chambers operating in the ionization range may be operated either as pulse-type or integrating instruments Proportional and Geiger regions are usually pulse-type. In most radiobiology laboratories, X- or gammarat exposures are measured with chambers operating in the ionizing region  R-meter is used for measurement  Consists of thimble-type ionization chamber and a separate charger-charge-reader unit Pulse-type chambers: used for counting individual ionizing particles or photons  Mostly operated in Geiger region to provide maximum pulse size per ionizing particle and minimum dependence on voltage stability Geiger-Muller, Geiger or G-M counter: has a wide application in tracer experiments and sometimes utilized in radiobiological studies with internal emitters. Proportional region pulse-type counters require a very stable voltage and not usually used in radiobiology for measuring radiation exposure.

Luminescent Dosimeters  Based on the idea that certain substances, which are not normally luminescent when treated in certain ways, can be made to give off light when treated by prior exposure to ionizing radiation  Photoluminescent system: in this typical system, silver-containing metaphosphate glass is exposed to radiation.  Some of the loosely bounded electrons which are released from the negative ions of the glass are trapped by silver ions.

When silver atoms are exposed to ultraviolet light, they absorb energy and fluoresce upon returning to stable ground state Thermoluminescent dosimetry: when a crystalline material composed of a phosphor, lithium fluoride, is exposed to ionizing radiation, electrons will be excited into higher energy levels.  When energy is applied in the form of heat, the trapped electrons return to the ground state with an emission of light.  Radiation exposure can be determined from the intensity of emitted light, Glass Rod dosimeter: consistes of a small rod 1 mm in diameter and 6 mm long 

 

Is a combination of paraffin was with chloroform-methyl yellow During exposure to radiation, its color changes from yellow to red in proportion to the amount of ionizing radiation absorbed Sensitivity of this dosimeter is low

Scintillation Detectors  When an ionizing particle or photon passes through a suitable crystal or liquid phosphor, energy is absorbed, resulting in excitation of electrons in the scintillator.  Energy is re-emitted as flashes of light or scintillations which are absorbed by photocathode of photomultiplier tube.  Photoelectrons are emitted and amplified by photomultiplier tube.  A current pulse is produce.  Detectors can measure the energy distribution of the incident radiations as well as counting them.  Can distinguish particles from different sources Calorimeters  Is a thermal or heating measuring device.  Can be used for measurement of the enrgy absorbed from radiation  Not very sensitive since the rate of heat production from most sources of radiation is very small  Suitable for  measuring radiation sources of high activity  determining the energy of particles produced by particle accelerators  Measurement of complex radiations from reactors Chemical Dosimeter  Fricke Dosimeter / Ferrous-Ferric System: a well oxygenated solution of pure ferrous ammonium sulfate in dilute sulfuric acid is exposed to radiation  Ferrous are oxidized to ferric ions in an amount which is dependent on the total amount of energy deposited in the system.  UV Spectrophotometer: determines the quantity of ferric ions produced  Potsaid-Irie Chemical Dosimeter: has been developed for the estimation of the distribution of the radiation exposure within a biological specimen

PHOTOGRAPHIC FILM -was one of the first radiation detectors -used for personnel monitoring and for visualization of gross or cellular localization of certain radionuclides Two types of film used 1. Film which can be calibrated for exposure in terms of gross blackening 2. Nuclear emulsion I which the tracks of ionizing particles can be visualized microscopically Silver halide suspended in a gelatin base ; usually silver bromide y Ionizing radiation s passing through the film produce free electrons which are trapped in the crystal lattice structure of the film and reduce the silver ions. y When the film is developed, silver bromide grains which contains silver ions are converted to grains of metallic silver y Fixer removes undeveloped silver salts y If there are sufficient number o grains developed, the film will appear to be grossly blackened. y With a special type of film, it I possible to detect and quantitate last neurons, thermal neutrons, electrons, alpha particles, and gamma or x-rays Autoradiography process in which the film can be used to study the localization of radionucides in tissue y If tissue from a plant or animal containing radionuclide is placed next

to a film , the radiation from decaying atoms of the radionuclide will expose the film y When the film is developed, the dark (exposed) areas of the film will correspond to the tissue areas of greatest concentration of radionuclide. Autoradiograms without separating the tissue and the film after exposure this technique is used for a more precise intraorgan or intracellular localization of the radionuclides, especially if a source of alpha or low-energy beta radiations is used Autoradiograph technique - determines the intraorgan and intracellular distribution - helps the radiobiologist to interpret puzzling tissue changes in light of the non uniform radiation exposure received by the tissue. y The tissue distribution of small quantities of radionuclides can be visualized. y The distribution is the same as the distribution of the stable isotopes of the same elements y This technique makes it possible to predict the behavior of stable elements under a variety of experimental treatment CLOUD CHAMBERS AND BUBBLE CHAMBERS - To visualize the passage of an ionizing particle or photon - Operation depends on the presence of a supersaturated region in a gas which contains a condensable vapor - When centers are absent, dust particles or ions, on which condensation can occur, the supersaturated condition can exist in practically no condensation occurring. - When centers occur, vapors condenses with them, producing visible spot. - Cannot detect or measure the radiations BUBBLE CHAMBER

Ions formed by the passage of ionizing radiations through a superheated liquid create condensation nuclei for the formation of bubbles. If the chamber is filled with a highdensity liquid, for this reason, the bubble chamber has its chief use with high-energy particle accelerators

DOSIMETRY Dosimeter use to detect the presence of radiation and to measure the radiation intensity The radiation exposure to various tissue of an animal. If an internal emitter is used as a radiation source, various organs can be removed and counted individually with a GEIGER OR SCINTILLATION SYSTEM Intraorgan distribution can be determined by autoradiography of the tissue MICRODOSIMETERS of glass rods or Lil types can be implanted in the tissue to measure exposure from either internal or external source R-meter used for dosimetry when the radiation source is external ; with relatively large size; should not be placed in direct contact with tissue Phantom to measure internal dose Water-filled or masonite blocks phantom, are used which have holes at appropriate spots into which the chambers are placed.

X-RAY DOSIMETRY Factors that influence the radiation dose which a tissue perceive : a. Depth of the tissue below the skin surface b. Thickness and type of material below the tissue c. Area of the radiation field d. Quality of the radiation (HVL)

e. Distance of the radiation source to the skin surface Air Dose dosimeter is positioned inn air at some specified location Surface Dose or Skin Dose exposure at the surface, specimen is introduced to a beam; can be measured by placing a dosimeter on the surface of the skin. Depth Dose exposure at some location within the specimen; can be measured with implanted dosimeter y The surface dose is greater than the air dose by the amount of radiation which is scattered back by the underlying material Low energy radiation there is considerably backscatter and the skin dose relative to the air dose is maximum Harder Radiation there is a greater tendency for scatter to be in a generally forward direction, therefore skin dose decreases. A larger field results in a higher surface dose due to side scatter Large-field size data radiobiologist more applicable to

Phantom measurements can be made with gamma radiation

Exposure of Biological Systems Factors to consider when irradiating a specimen 1. Total dose required 2. Desired distribution of dose within the system 3. Type of radiation 4. Dose rate required Experimental arrangements Gamma irradiation cells are suitable for irradiation of relatively small specimen when a high exposure rate is required. - Chemical Solutions, microorganism, or small seeds are positioned in the cell. Using remote control manual manipulators an operator working from the outside the cell removes pencil containing Cobalt-60 from a shielded well which is one corner of the room. 2. Rats receiving a total body radiation exposure from 250kvp x-ray machine. The exposure rate in air is determined with a Victoreen R-chamber placed in one of the sections of the wheel - X-Ray machines is also suitable for partial body or localized irradiation 1.

Isodose Charts can be constructed for any desired combination of characteristics and are commonly used in radiation therapy to estimated depth dose. Depth dose distribution markedly influenced by the energy of the incident radiation Gamma rays monoenergetic; consist of photons with a limited number of differet strategies.

Without the soft radiation component of most x-ray beams, the gamma rays have less backscatter and greater penetration

CHAPTER 4 RADIATION CHEMISTRY

DIRECT VS. INDIRECT EFFECT INDIRECT EFFECT OF RADIATION important in aqueous systems where a water molecule may be ionized and then may transfer its acquired energy to another molecule IONIZATION AND EXCITATION TWO MAJOR MECHANISMS FOR ENERGY TRANSFER a. b. IONIZATION orbital electron is ejected from the molecule EXCITATION electron is raised to a higher level

1.

2.

3.

When an electron is ejected from a molecule, the result is positive ion (A+) and a negative electron (e-), both of which contain a great deal of energy. The electron cant exist free for very long and is rapidly captured by another molecule to yield a negative ion (B-). The overall result of these events is the formation of 2 ions, 1 negative and 1 positive.

ION PAIRS positive ion and the negative ion *relative electron affinities of molecules near the ejected electron will determine which one will capture the electron and become the negative ion. CHARGE NEUTRALIZATION electron is recaptured by the positive ion from which it was ejected FORMATION OF FREE RADICALS *ion pairs last only a very short time FREE RADICALS intermediaries between ion pairs and final chemical products; extremely reactive as a result of an unpaired electron in one of their outer orbits; electrically neutral molecule which has an unpaired electron in the outer orbit; extremely reactive y A number of radical reactions are possible depending on the concentration of the radicals themselves

AVERAGE ENERGY LOSS FOR IONIZATION average of one ionization occurs for each 32.5 electron volts(ev) dissipated in the system IONIZATION POTENTIAL actual amount of energy needed to eject an electron from a molecule -ranges from 10ev to 25ev *ionizations are seldom produced singly, but rather as double or triple events RADIATION CHEMICAL YIELDS USED TO COMPARE AND WUANTITATE THE RADIATION EFFECT ON CHEMICAL SYSTEMS a. G value number of molecules changed per 100ev transferred to a system; represents the number of radicals formed for each primary ionization G- # of molecules changed / 100ev

RADIOCHEMISTRY OF WATER y b. M/N value or IONIC YIELD number of molecules changed per ionization M/N = # of molecules changed/ of ionizations Most biological systems are about 80% water

CURIE AND DEBIERNE observed the evolution of oxygen and hydrogen gases from a solution of radium salts MASS SPECTROMETER used to determine the ions formed by the impact of electrons on water vapour; demonstrated the presence of HO2+, HO+ and H2O+ ions and small amounts of H2+ and O+ ions in the bombarded vapour

32.5 ev are expended each time an ionization occurs; G= 3M/ N FORMATION OF ION PAIRS

RADIOLYSIS irradiation breakdown HYDROGEN PEROXIDE FORMATION HYDROGEN PEROXIDE active oxidizing agent HO2- - anion of H2O2 PRODUCTION OF H2O2 IN AQUEOUS SYSTEM: 1. With pure water and no O2, there is little measurable H2O2 since that which is formed is destroyed by the free radicals present. With material such as acrylamide present that will react with free radicals, but with no O2 present, some H2O2 can be measured. In the presence of oxygen, additional H2O2 will be formed. In the presence of oxygen plus additives which are oxidized by HO2, the production of H2O2 will be high.

When OH and H radicals are formed in irradiated aqueous solutions, a certain proportion of these will recombine to form H2O or will combine in the molecular reactions to form H2 and H2O2. Concentration of solute is low = radicals reacts with each other, so that the yield (extent of reaction of solute molecules) will be low Concentration of solute molecules increases = probability of an OH or H radical reacting with the solute molecule increasesd

2.

3. 4.

INTERACTION OF FREE RADICALS WITH SEVERAL SOLUTES y When more than one type of solute molecule is present in a solution, the free radicals will react most readily with those that are largest in size, those that are most numerous, and those that are most reactive.

RADIATION EFFECTS ON SIMPLE CHEMICAL SYSTEMS y When ionizing radiation impinges on a system, the molecules ionized will be those which are actually in the path of the radiation, without regard for their chemical composition or reactivity. The H, OH and HO2 radicals which are formed by the irradiation of water molecules can have a variety of effects on other molecules present in the system.

DIRECT VS. INDIRECT EFFECT IN AQUEOUS SOLUTIONS y The indirect effect of radiation on the solute in an aqueous system involves changes in the solute molecules secondary to the formation of free radicals from the water molecules As the radiation dose is doubled the number of ion pairs formed, the number of free radicals formed, and the number of solute molecules affected are doubled. If a solution is frozen, the mobility of the radicals which are produced in the water molecules is decreased. The dose required to produce a chemical change in a given proportion of the molecules of a substance, by direct action, is inversely proportional to the molecular weight of the substance

H radical powerful reducing agent, readily gives up its unpaired electron OH radical - is an oxidizing agent HYDROXYL RADICALS initiate polymerization, add at double bonds of organic compounds, reduce powerful oxidizing agents and remove hydrogen atoms from organic molecules. INTERACTION OF RADICALS WITH A SINGLE SOLUTE y

REACTIONS IN AQUEOUS INORGANIC SOLUTIONS

In simple organic solutions, the primary reactions are reduction of cations and anions by H radicals and oxidation of cations and anions by OH and HO2 radicals and by H2O2.

INTERMOLECULAR CROSSLINKING becoming attached to itself INTERMOLECULAR CROSSLINKING attachment between different molecules PEPTIDE CHAIN primary structure of protein CHANGES IN PROTEINS UPON IRRADIATION 1. 2. 3. 4. y Increase/ decrease in viscosity Changes in refractive index Optical rotation Electrical conductivity All enzymes can be inactivated when irradiated in solution

REACTIONS IN AQUEOUS ORGANIC SOLUTIONS y When an aqueous solution is irradiated, the usual indirect reaction on the organic molecule is the removal of either a H atom or an entire radical group from the molecule.

REACTION WHICH WILL PRODUCE A DIFFERENT MOLECULAR SPECIES 1. 2. 3. Condensation 2 radicals combine Rearrangement 2 radicals combine and then split into 2 diff. forms Combination

GENERAL REACTIONS 1. Most saturated hydrocarbons probably undergo a hydrogen extraction, and are converted to alcohols in a 2 step process. Acetic acid most frequently loses a hydrogen atom attached to the methyl group and 2 of the resulting radicals condense to form succinic acid. In the presence of oxygen, a rearrangement occurs with the radical form to give glycolic acid and glyoxylic acid. Irradiation of aqueous methanol or ethanol will lead to the production of aldehydes and glycols by similar steps.

NUCLEIC ACID macromolecules w/c are considered to be the carriers of genetic info.; composed of nitrogenous bases: a. purines b. pyrimidines TYPES OF DAMAGE TO DNA MOLECULES 1. 2. 3. 4. 5. 6. 7. 8. Change of base 2. Loss of a base 3. Hydrogen bond breakage between chains Single-strand fracture Double-strand fracture Cross-linking within the helix Crosslinking to other dna molecules Crosslinking to proteins

2.

3.

*pyrimidine bases are more radiosensitive than purine bases *thymine is the most sensitive of the pyrimidines

MACROMOLECULAR REACTIONS DEGRADATION breaking into smaller units; occur when large molecules are irradiated HAEMOCYANINS giant protein molecules in the blood of certain arthropods and mollusks CROSSLINKING another common structural change

CHAPTER 5
TheCell_____________________

 Cell Theory -Proposed by Schleiden and Schwann 1838 -All living systems are composed of either small units called cells  Electron Microscope -Tool for cytologic study -Provides high degree of resolution  Steady State - More than the minimum amount of energy that a cells need.  Absorption and Utilization of Energy - Plant systems use and store energy of light & produce food through the process called photosynthesis. - Animals cannot use light energy directly, but must obtain their ochoenergy-supplying food and substances by eating plants or plant products. Most cellular activities appear to occur in or on specific structure & portion of cell

Site of important enzyme function. - Site of ATP production.  Lysosome - Contain number of the digestive or degradative enzyme of the cell. -

Effects of Radiation to Cell________  Large doses of radiation (30005000 rads) - Produce dramatic changes in the membrane of cell. - Plasma membranes are ruptured - membranous structure of the ER is dilated. - Mitochondria often appears swollen and the internal membranes are disorganized.  Goldfeder - Suggested that some of these changes may be due to altered permeability of the mitochondrial membranes.  Enzyme-release-Hypothesis - Proposed by bacq& alexander (1961) - States the significance of intracellular barriers in maintaining the integrity and viability of cell. - Presence of protolytic enzymes and nucleic acid attacking enzyme in the lysosomes of the cells and the fact that these enzymes are normally released when

 Plasma Membrane - Limiting structure of the cell and composed of lipoprotein complex.  Endoplasmic Reticulum - Continuous intracellular membrane network forms an interconnecting series of channel inside the cell.  Mitochondria

a cell dies to act on and digest cellular constituents. Effects of Radiation to cell metabolism  Phosphorylation is reduced as well as ATP production.  Decrease in phosphorylation is due to uncoupling of phosphorylation mechanism from those of oxidation. Radiation effects on enzyme_____  High doses of radiations are required to inactivate enzymes in invitro.  Alteration of enzymatic activity in biological system have been demonstrated , the radiation doses required higher dosage than those which produce mutations or chromosome damage. Radiation effect on synthetic processes  A decrease in the rate of DNA synthesis following radiation has been reported in experiments which measure the rate of cellular incorporation of radioisotopelabeled precursor of DNA.  The synthesis of RNA may be delayed or depressed by irradiation.  Delays mitotic activity Effects of radiation to Chromosome_  In the late 1920s, researchers discovered another kind of biological effect from ionizing radiation: damage to genes and chromosomes. Some of this damaged genetic material may be

transmitted to future generations. In this section and the next, some rudimentary facts about genes and chromosomes are summarized.  Every cell contains thousands of genes. They are housed in a small number of thread-like bodies called chromosomes, usually located in the nucleus of the cell. Chromosomes are visible under a microscope, but genes are not. Each gene is sited at a precise location along its thread-like chromosome.  A cell having no direct role in sexual reproduction is called a "somatic" cell. It normally contains twice as many chromosomes as a reproductive cell. In humans, for instance, a somatic cell typically has 46 chromosomes, whereas a sperm or egg has only 23. When sperm meets egg, the fertilized egg gets two sets of 23 chromosomes for a total of 46. This is the first somatic cell of a new human being. It has its own unique combination of genes, which will determine the inherited physical characteristics of the developing offspring.  All the genetic material in a somatic cell is meticulously duplicated just before it undergoes normal cell division. Then, when the cell cleaves in two, a complete duplicate set of 46 chromosomes is given to each of the two daughter cells. This process is known as "mitosis". As the foetus grows, every somatic cell in its body gets an identical copy of the original 46 chromosomes inherited from its parents -- if nothing goes wrong.

 Reproductive cells are formed by a different sort of cell division called "meiosis", occuring only in the gonads. In meiosis, the 46 chromosomes of a somatic cell are not duplicated but segregated into two equal sets of 23 chromosomes shortly before cell cleavage. Then each daughter cell receives only 23 chromosomes, becoming either a sperm or an egg, able to participate in sexual reproduction to produce further offspring. In this way, half of the genetic material originally inherited from one's parents may be passed on to one's own child, who can in turn pass some of it on to his or her descendents.  A mutagen is any agent causing damage to genetic material. Genetic damage falls into two main categories: 1. chromosome aberrations, involving changes in the number or structure of chromosomes; 2. alterations of the genes themselves, called "gene mutations".  Most chromosome damage is visible, often involving some form of breakage. A "deletion" occurs when a segment of a chromosome is broken off and lost.  An "inversion" occurs when the broken segment reattaches, but in the reverse order.

chromosome attaches itself to a different chromosome.  A "reciprocal translocation" occurs when two broken segments from two chromosomes reattach, but each to the wrong chromosome. Ring chromosomes, dicentric chromosomes and other abnormal chromosomes may be formed in a similar fashion.

 Chromosome damage can have serious medical consequences. In the 1960s, it was discovered that specific chromosome deletions give rise to the "cri-du-chat" syndrome and the "Wolf-Hirschhorn syndrome" in humans -- two hereditary disorders involving severe mental retardation, stunted growth and a delay in psychomotor development.  A loss of genetic material, such as the deletion of part of a chromosome, might be expected to cause problems. But too much genetic material can be just as damaging as too little. If either the sperm or egg happens to contain an extra chromosome (24 instead of 23), the fertilized egg ends up with 47 chromosomes rather than 46. Instead of 23 pairs of matched chromosomes -- one of each type from each parent -- there are 22 pairs and a triplet. This condition is called a "trisomy".  Since 1959, four hereditary human diseases have been linked to specific trisomies. They are "Down's syndrome", "Edwards' syndrome", "Patau's syndrome" and the "Cat-Eye syndrome".

 A "translocation" occurs when a broken segment from one

 Even chromosome aberrations involving no excess or deficiency of genetic material can have debilitating consequences. Some children displaying full-blown symptoms of Down's or Edwards' or Patau's syndrome do not exhibit any trisomies in their somatic cells. Instead they show translocations affecting the very same chromosomes which are trisomic in most other cases of these genetic diseases.  By contrast, a gene mutation causes no visible damage to the chromosome. There are two types of gene mutations: dominant and recessive. The effect of a dominant mutation can be seen in any offspring inheriting the mutant gene from either parent. The effect of a recessive mutation is not fully expressed in the offspring unless the same mutant gene is inherited from both parents.  Thus a dominant mutation carried in sperm or egg will be expressed in the first generation offspring, whereas a recessive mutation may not become apparent for many generations. It may take a long time indeed before a sperm and an egg, both carrying the same mutant gene, happen to meet.

Chromatid Type Aberration Nearly all the aberrations we see with solid staining appear to result from the interaction ("re-joining") of two breaks, so we can further classify them on the basis of where these breaks are situated in relation to the chromosome arms (Savage, 1976). - If the breaks are situated in the arms of different (non-homologous or homologous) chromosomes we have the category of INTERCHANGES. - If the breaks are in the opposite arms of the same chromosome, we have the category of INTER-ARM INTRACHANGES. - If the two breaks are both in the same arm of a chromosome, we have the category of INTRA-ARM INTRACHANGES. These three categories are often referred to collectively as EXCHANGES.

CHAPTER 6
RADIATION GENETICS *Genetics- study of heredity *Mutation- alteration in any specific linear sequence and changes the information passed on; focuses in phenotype change or survival of the progeny. *Progeny-genetic descendant or offspring. *Haploid (n)- no. of chromosomes of postmeiotic sex cells; man=23n. *Somatic cells are usually diploid *homozygous- if the diploid cells contain identical genes at a given locus. *heterozygous- if the genes on the two chromosomes differ at the locus. *dominant mutations- expressed in the immediate descendants of the mutated cell. *Genetic mutation- where mutation occurred in the germ cells *Somatic mutation- where mutation occurred in the daughter cells of dividing somatic cells. *Recessive mutations- only expressed if both chromosomes of the cell contain the mutation; or no dominant gene to mask the recessive characteristic. GENETIC MUTATIONS *H.J. Muller- reported the occurrence of true genes; studied the irradiated sperm of Drosophila melanogaster; wrote the Artificial Transmutation of the Gene ; found that the heaviest x ray dose is found in the X chromosome; found the x-ray mutagenesis. *Goodspeed& Olson- studied irradiated mature plants of Nicotiana (tobacco plants)

*Stadler- used x-irradiation in maize and barley; interpreted the mutations due to chromosome aberrations rather than gene mutations.

*Wild-type E. coli- grows only on medium made up of salts, water, and carbon source. *Other examples of microorganisms studied for mutations are tobacco mosaic virus, Neurospora; other organisms: Arabidopsis, Habrobracon (wasp), and mice. MUTATIONS IN MAN *Gene loci differ markedly in their mutability. *Mitotic stage, cell type, sex species, and dose rates influence the rate of mutation production. *Hiroshima and Nagasaki descendants- largest group of humans for study of exposed radiation. *Radiation exposure will increase the mutation rate in man. *Doubling dose for Man: 10-100 rads *Acute irradiation: 15-30 rads *Chronic irradiation- around 100 rads SOMATIC MUTATIONS *Somatic mutations- mutations not in germ cells; the mutant genes are NOT passed on to offspring; occur spontaneously; example of this is the color change in plants (e.g. flowers) *Patterson- reported somatic mutations in Drosophila. *Somatic mutations may contribute to long-term effects of irradiation in mammals such as formation of tumors.

Mutation Studies in Drosophila Muller measured recessive mutations in studies of radiation effects in Drosophila. Recessive lethal on the in the X chromosome are especially useful for study since they are carried w/o adverse effect in the heterozygous state in females while in males presence of this result to death. ClB method was used by Muller in studying Drosophila w/c contains three specific characteristics on the X chromosome. The crossover suppressor (C) maintains the integrity of the X chromosomes. The same X chromosomes contains a recessive lethal mutation (l), insuring all males inherit the chromosome will die, and a dominant visible marker, Bar (B), w/c reduces the width of the eyes of all flies in w/c it is found.

*All the F2 male flies come from a single sperm of an irradiated male in the F0 generation, wild type males will also be non-viable and there will be no males at all in F2.

Muller-5 (M-5) method is the second technique for detecting sec-linked, recessive lethal mutations. This is similar in the principle to the ClB method, the only difference is that instead of using lethal mutation a recessive visible marker (eye color mutation apricot). Females which are homozygous for this M-5 chromosomes are mated to irradiated wild-type males.

* Normal Drosophila

*Absence of the latter group indicates a recessive lethal mutation induced by radiation. If there is no mutation, the offspring appear normal since they are heterozygous for the recessive genes. If irradiation has produced a mutation at one of the gene loci in the male, the offspring will show a mutant phenotype.

Mutation of the wings Mutations of the antennae

Experimental Results Points emerged 1. Spontaneous mutations w/c would arise w/o radiation. 2. Radiation-induced mutations

Most of the experiments done also indicate that the mutation frequency is substantially linear with increasing dose.

of ejaculation) Spermatozoa (w/in inseminated females)

FEMALE
Oogonia and early oocytes Late oocytes (last 3-4 days)

1 2-3

POST FERTILIZATION *Production of a point mutation in Drosophila spermatozoa resulted from a single interaction of radiation w/ genetic material and that such a lesion was fixed immediately and could not be altered or repaired by subsequent treatment.
Immediate (within 10-25 minutes after egg laying) Cleavage

<1 < or equal to 12

RELATIVE FREQUENCIES OF RECESSIVE LETHAL MUTATIONS IN Drosophila PRODUCED BY A GIVEN DOSE OF RADIATIONS

*In all the experiment concluded the both induced and spontaneous mutations are overwhelmingly detrimental in character. However, in some situations where homogeneous material has been irradiated, the heterozygosity w/c resulted from the radiation has apparently resulted in a higher likelihood of survival. It is doubtful that such results can be called beneficial in respect to human population.

Stage

Relative Number Mutations Produced

MALE
Spermatogonia and early spermatocytes Meiotic division stages Spermatids Spermatozoa (more than 1 day pre-ejaculation) Spermatozoa (w/in 1 day 1 8 12 3 4-4.5 5-6