RAD251 Radiation Biology Comprehensive Study Guide

RAD251: Introduction to Radiation Biology

• Radiation Biology Definition: An interdisciplinary field of science studying the effects of radiation (both ionizing and non-ionizing) on biological materials. It encompasses various specialized areas:     * Radiation Physics: The study of the physical properties and interactions of radiation.     * Radiation Chemistry: The study of the chemical effects of radiation on living matter, such as the radiolysis of water.         * Example: Water radiolysis: $H_2O \xrightarrow{\text{radn}} H^+ + OH^-$. It also involves the formation of the hydrated proton ($H_3O^+$) and hydroxyl radicals.     * Molecular and Cellular Biology: Studying the interaction of radiation with molecular systems such as protein biosynthesis, DNA, and RNA.     * Molecular Biology: Studies the molecular underpinnings of transcription and translation of genetic materials.     * Cell Biology (Cytology): Focuses on the structure and physiology of cells and their interaction.     * Molecular Genetics: Studies the structures and functions of genes at the molecular level and the transfer of genes from generation to generation, including mutations.     * Cell Death and Apoptosis: Cell death occurring in a programmed cellular manner. Signs include cell shrinkage, loss of membrane, nuclear fragmentation, and DNA/chromatin fragmentation.     * Dose Modifiers: Includes radioprotectors and radiosensitizers.     * Bioelectromagnetics: The study of how electromagnetic (EM) fields interact with and influence biological processes. Examples include animal navigation using geomagnetic fields and the effects of man-made EM fields from power distribution systems and mobile phones.

Cell Theory and Biological Organization

• The Cell: Consists of the nucleus and the cytoplasm. The hierarchy of biological organization is: Cell \rightarrow Tissue \rightarrow Organ \rightarrow System.
• Cell Components (Cytoplasm): Includes Mitochondria, Endoplasmic Reticulum (ER), Golgi apparatus, Centrioles ($8\,nm$), and the Nucleus.
• Historical Development of Cell Theory:     * 17th Century: Discovery of the microscope.     * 1665: Robert Hooke (English physicist) described cork and plant cells, introducing the term "cells" because they reminded him of the blocks of cells occupied by monks. He published this in 1672.     * 1673: Antonie van Leeuwenhoek (Dutch) discovered blood cells and spermatozoa.     * 1830s: Improved microscopes with better lenses and higher magnification allowed for further discovery.     * 1833: Robert Brown (Scottish botanist) described the plant cell nucleus.     * 1839: Theodore Schwann (German physiologist) and Mathias Schleiden (German biologist) stated that cells are the elementary particles of organisms in both plants and animals.
• Fundamental Principles:     * The cell is the basic unit of life containing fundamental molecules.     * The nucleus is the "heart" of the cell.     * The cytoplasm is a homogeneous colloidal substance consisting of water, electrolytes, proteins, enzymes, carbohydrates, lipids, and soluble RNA.     * A human being is composed of over $75 \times 10^{12}$ cells.     * Cells contain carbon atoms which combine with four other atoms to form chains and rings involving $H_2$, $O_2$, and $N_2$. Small molecules (sugars, amino acids, nucleotides, fatty acids) form macromolecules:         * Polysaccharides: From sugars (starch, glycogen).         * Proteins: From amino acids. Formed into globular, compact shapes by specific sequences.         * DNA and RNA: From nucleotides.         * Lipids: From fatty acids.

Genetic Code and Heredity

• DNA: The hereditary apparatus for cell reproduction, carrying genetic information in a double-stranded (double helix) structure within chromosomes.
• RNA: Single-stranded but capable of self-replication. Some mRNA serves as messengers, others as catalysts. Ribosomes translate mRNA to protein using the genetic code.
• Genetic Code: The sequence of nucleotides in DNA/RNA that determines the amino acid sequence of proteins.     * RNA Nucleotides: Adenine (A), Guanine (G), Cytosine (C), and Uracil (U).     * Codon: Three adjacent nucleotides coding for an amino acid. There are $64$ total codons.         * $3$ codons do not code for amino acids but indicate the end of a protein.         * $61$ codons specify the $20$ amino acids.         * Degeneracy: Most of the $20$ amino acids are coded for by more than one codon.         * AUG Sequence: Codon for methionine and signifies the beginning of mRNA.     * The genetic code is identical in almost all species, with rare divergences in some mitochondria and certain eukaryotes.

Physics of Radiation and Interaction with Matter

• Radiation Definition: A form of energy that travels in a vacuum.
• Types of Radiation:     1. Electromagnetic (Ionizing): X-rays and gamma rays.     2. Particulate (Ionizing): $\alpha$, $\beta$ particles, neutrons, and protons.     3. Non-ionizing: Infrared, visible light, and UV rays.
• Mechanisms of Interaction:     * Ionization: Radiation has enough energy to knock electrons off atomic orbits, leaving a positive "hole." Together they form an ion pair. Formation of an ion pair requires about $34\,eV$.     * Excitation: Photon energy is not enough to knock off an electron but raises it to a higher energy level.     * Charged Particles: Interact with orbital electrons via electrostatic fields.     * Neutrons: Have no charge. Interaction is by direct collision with atomic nuclei. They can penetrate deep into matter.         * Maximum Interaction: Occurs when a neutron collides with a hydrogen nucleus ($H^+$) because they have similar mass.         * Biological tissue is high in hydrogen (water, proteins, fluids), making neutron interaction highly significant and damaging.     * Energy Deposition: As radiation passes through matter, its energy and speed fall while the number of interactions per unit length increases.
• Law of Bergonié and Tribondeau: The radiosensitivity of biological tissues is directly proportional to mitotic activity and inversely proportional to the degree of differentiation of the cells.

Levels of Radiobiological Damage

1. Sub-cellular: Damage to cell membranes, nucleus, chromosomes, mitochondria, and lysosomes.
2. Cellular: Inhibition of cell division, cell death, and malignant transformation.
3. Molecular: Damage to macromolecules (enzymes, RNA, DNA) and interference with metabolic pathways.
4. Tissue-organ: Systemic damage to the CNS, bone marrow, and GIT, resulting in death or cancer induction.
5. Whole Animal: Death and life-shortening.
6. Population of Animals: Genetic and chromosomal mutations leading to changes in population characteristics.

Measurement of Ionizing Radiation

• Roentgen (R): Unit of Exposure ($X$). The amount of X or gamma radiation such that the associated corpuscular emission per $0.001293\,gramme$ of air produces ions carrying one electrostatic unit of charge ($esu$) of either sign.     * $1\,R = 2.58 \times 10^{-4}\,C/kg$ of air.
• Rad: Unit of Absorbed Dose. Energy absorbed per unit mass ($100\,erg/g$).
• Gray (Gy): SI unit of Absorbed Dose.     * $1\,Gy = 100\,rads$.     * $1\,R = 0.869\,rad$ of absorbed dose in air.
• Rem: Unit of Dose Equivalent.     * $\text{Dose Equivalent} = \text{Absorbed Dose (rads)} \times \text{Quality Factor (Q)}$.     * Definitional standard: Same biological effect as $1\,rad$ of Cobalt-60 gamma rays.
• Sievert (Sv): SI unit of Dose Equivalent.     * $1\,Sv = 100\,Rem$.
• Curie (Ci): Unit of Activity. The number of disintegrations per second.     * $1\,Ci = 3.7 \times 10^{10}\,\text{disintegrations per second}$.
• Effective Dose (E): The product of the dose equivalent and tissue weighting factor ($W_T$).     * $\sum W_T = 1$ for the whole body.
• Collective Dose: Product of average effective dose and the total number of people in the population. Unit: Person-Sievert.

Specific Assessment Methods for Absorbed Dose

• Calorimetric Method: Based on temperature rise ($\Delta T$) proportional to absorbed energy.     * Drawback: Rise is very small ($1\,Gy$ produces only $2 \times 10^{-4}\,^{\circ}C$), requiring sensitive instrumentation.
• Air Ionization Chamber: Based on ionization causing current flow. Needs specific design for accuracy:     * Guard Ring/Annulus: Separated electrodes ensure a defined volume of air (region ABCD) where electric field lines are parallel.     * Electronic Equilibrium: Average electron loss equals gain in the measurement volume.     * Voltage: Potential difference must be high enough to collect all ion pairs (saturation).     * Plate Separation ($d$): Must be large enough to allow all secondary ionizations to occur. Ranges from $20\,cm$ for $250\,keV$ to several meters for $1\,MeV$. Limited to energy below $3\,MeV$.     * Correction Factor: Calculation must correct for Temperature ($T$) and Pressure ($P$):         * $R'' = R \times \frac{T+273}{293} \times \frac{760}{P}$
• Chemical Method (Fricke's Method): Based on radiation oxidizing ferrous sulfate ($FeSO_4$) to ferric sulfate ($Fe_2(SO_4)_3$).     * Requires large doses (exceeding $20\,Gy$) due to low sensitivity. Yield: $15$ ferric ions per $100\,eV$.

Properties and Characteristics of X-Rays

• Physical Properties: Invisible, electrically neutral (not deflected by fields), zero mass, travels in a straight line at the speed of light, cannot be focused optically, poly-energetic/heterogeneous.
• Interactions:     * Photon-Nucleus: Photodisintegration or annihilation.     * Photon-Electrostatic Field: Pair production.     * Photon-Orbital Electron: Includes Thomson scattering, Coherent (Rayleigh) scattering, Compton effect, and Photoelectric effect ($\tau$).     * Photoelectric Cross-Section ($\tau$): $\tau(h\nu, Z) = K \frac{Z^n}{(h\nu)^3}$, where $n$ is between $3.6$ and $5.3$.

Personnel Monitoring and Dosimetry

• ALARA Principle: As Low As Reasonably Achievable (per ICRP 26, 1997).
• Film Badge: Uses photographic effects to determine dose via optical density.     * Filters:         1. Open Window: Beta particles.         2. Thin Plastic ($50\,mg/cm^2$): Beta.         3. Thick Plastic ($300\,mg/cm^2$): Absorbs Beta.         4. Dural ($Al + Cu$ alloy).         5. Tin + Lead: Determines high vs. low energy photons.         6. Cadmium + Lead: Detects slow neutrons (Cadmium captures neutrons and emits gamma rays).         7. Lead Edge: Shielding.         8. Indium Foil: Criticality indicator (activates at doses above $10\,mSv$).     * Emulsions: Fast (records small exposures) and Slow (records high exposures/accidents).
• Thermoluminescent Dosimeter (TLD): Based on light emission when heated.     * Mechanism: Radiation traps excited electrons in the "Forbidden band" between the Valence and Conduction bands. Heating releases these electrons to the ground state, emitting light.     * Materials:         * Lithium Fluoride (LiF): Effective atomic number ($Z=8.31$) is close to soft tissue ($Z=7.42$). Used in clinical medicine.         * Calcium Fluoride ($CaF_2$): Higher $Z$, used for Cobalt-60 radiation; shows rapid variation at lower energies.     * Advantages: Wide dose range ($10^{-5}$ to $10^{3}\,Gy$), reusable after annealing, rapid reading, small size.
• Clinical Safety - The 10-Day Rule: Radiological exams of the lower abdomen in females of childbearing age should be done within $10$ days of the last menstrual period (LMP) to avoid fetal irradiation before the egg is released (typically day $14$).     * Exceptions: Sterility, contraceptives (not less than 10 days), no sexual intercourse, or overriding clinical necessity for the mother's life.

Radiation Detectors Comparison

• Ionization Chamber: Quantitative, measures exposure rate or absorbed dose, can indicate energy.
• Geiger-Müller (GM) Counter: Qualitative, measures counts per minute (cpm/cps), used for area monitoring and contamination detection.
• Scintillation Detectors: Used for activity measurements and surveys. Give readings in cpm/cps.
• Solid State Detectors: Semi-conductors (e.g., Diffused junction diode, Lithium drifted) that increase in conductivity when irradiated.