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Basic Radiobiology Chapter 14: Basic Radiobiology Set of 88 slides based on the chapter authored by N. Suntharalingam, E.B. Podgorsak, J.H. Hendry of the IAEA publication (ISBN 92-0-107304-6): Radiation Oncology Physics: A Handbook for Teachers and Students Objective: To familiarize the student with the basic principles of radiobiology. Slide set prepared in 2006 by E.B. Podgorsak (Montreal, McGill University) Comments to S. Vatnitsky: [email protected] Version 2012 IAEA International Atomic Energy Agency CHAPTER 14. TABLE OF CONTENTS 14.1. Introduction 14.2. Classification of radiations in radiobiology 14.3. Cell cycle and cell death 14.4. Irradiation of cells 14.5. Type of radiation damage 14.6. Cell survival curves 14.7. Dose response curves 14.8. Measurement of radiation damage in tissue 14.9. Normal and tumour cells: Therapeutic ratio 14.10. Oxygen effect 14.11. Relative biological effectiveness 14.12. Dose rate and fractionation 14.13. Radioprotectors and radiosensitizers IAEA Radiation Oncology Physics: A Handbook for Teachers and Students - 14. 14.1 INTRODUCTION Radiobiology is a branch of science which combines the basic principles of physics and biology and is concerned with the action of ionizing radiation on biological tissues and living organisms. Study of basic radiobiological mechanisms deals with biological effects produced by energy absorption in small volumes corresponding to single cells or parts of cells. IAEA Radiation Oncology Physics: A Handbook for Teachers and Students - 14.1 Slide 1 14.1 INTRODUCTION All living entities are made up of protoplasm, which consists if inorganic and organic compounds dissolved or suspended in water. The smallest unit of protoplasm capable of independent existence is the cell, the basic microscopic unit of all living organisms. IAEA Radiation Oncology Physics: A Handbook for Teachers and Students - 14.1 Slide 2 14.1 INTRODUCTION Group of cells that together perform one or more functions is referred to as tissue. Group of tissues that together perform one or more functions is called an organ. Group of organs that perform one or more functions is an organ system or an organism. IAEA Radiation Oncology Physics: A Handbook for Teachers and Students - 14.1 Slide 3 14.1 INTRODUCTION Cells contain: • Inorganic compounds (water and minerals) • Organic compounds (proteins, carbohydrates, nucleic acids, lipids) The two main constituents of a cell are the cytoplasm and the nucleus: • Cytoplasm supports all metabolic functions within a cell. • Nucleus contains the genetic information (DNA). IAEA Radiation Oncology Physics: A Handbook for Teachers and Students - 14.1 Slide 4 14.1 INTRODUCTION Human cells are either somatic cells or germ cells. Germ cells are either a sperm or an egg, all other human cells are called somatic cells. Cells propagate through division: • Division of somatic cells is called mitosis and results in two genetically identical daughter cells. • Division of germ cells is called meiosis and involves two fissions of the nucleus giving rise to four sex cells, each possessing half the number of chromosomes of the original germ cell. IAEA Radiation Oncology Physics: A Handbook for Teachers and Students - 14.1 Slide 5 14.1 INTRODUCTION When a somatic cell divides, two cells are produced, each carrying a chromosome complement identical to that of the original cell. New cells themselves may undergo further division, and the process continues producing a large number of progeny. IAEA Radiation Oncology Physics: A Handbook for Teachers and Students - 14.1 Slide 6 14.1 INTRODUCTION Chromosome is a microscopic, threadlike part of a cell that carries hereditary information in the form of genes. Every species has a characteristic number of chromosomes; humans have 23 pairs (22 pairs are non-sex chromosomes and 1 pair is sex chromosome). Gene is a unit of heredity that occupies a fixed position on a chromosome. IAEA Radiation Oncology Physics: A Handbook for Teachers and Students - 14.1 Slide 7 14.1 INTRODUCTION Somatic cells are classified as: • Stem cells, which exists to self-perpetuate and produce cells for a differentiated cell population. • Transit cells, which are cells in movement to another population. • Mature cells, which are fully differentiated and do not exhibit mitotic activity. IAEA Radiation Oncology Physics: A Handbook for Teachers and Students - 14.1 Slide 8 14.2 CLASSIFICATION OF RADIATIONS IN RADIOBIOLOGY Radiation is classified into two main categories: • Non-ionizing radiation (cannot ionize matter). • Ionizing radiation (can ionize matter). Ionizing radiation contains two major categories • Directly ionizing radiation (charged particles). electrons, protons, alpha particles, heavy ions. • Indirectly ionizing radiation (neutral particles). photons (x rays, gamma rays), neutrons. IAEA Radiation Oncology Physics: A Handbook for Teachers and Students - 14.2 Slide 1 14.2 CLASSIFICATION OF RADIATIONS IN RADIOBIOLOGY In radiobiology and radiation protection linear energy transfer (LET) is used for defining the quality of an ionizing radiation beam. In contrast to the stopping power, which focuses attention on the energy loss by a charged particle moving through a medium, LET focuses attention on the linear rate of energy absorption by the absorbing medium as the charged particle traverses the medium. IAEA Radiation Oncology Physics: A Handbook for Teachers and Students - 14.2 Slide 2 14.2 CLASSIFICATION OF RADIATIONS IN RADIOBIOLOGY ICRU defines LET as follows: “LET of charged particles in a medium is the quotient dE / d where dE is the average energy locally imparted to the medium by a charged particle of specified energy in traversing a distance of d .” IAEA Radiation Oncology Physics: A Handbook for Teachers and Students - 14.2 Slide 3 14.2 CLASSIFICATION OF RADIATIONS IN RADIOBIOLOGY In contrast to the stopping power, which has a typical unit of MeV/cm, the unit reserved for the LET is keV/ m . Energy average is obtained by dividing the particle track into equal energy increments and averaging the length of track over which these energy increments are deposited. IAEA Radiation Oncology Physics: A Handbook for Teachers and Students - 14.2 Slide 4 14.2 CLASSIFICATION OF RADIATIONS IN RADIOBIOLOGY Typical LET values for commonly used radiations are: Radiation LET (keV/ m ) • 250 kVp X rays 2 • Cobalt-60 rays 0.3 • 3 MeV X rays 0.3 • 1 MeV electrons 0.25 LET values for other, less common radiations are: Radiation LET (keV/ m ) • 14 MeV neutrons 12 • Heavy charged particles 100 – 200 • 1 keV electrons 12.3 • 10 keV electrons 2.3 IAEA Radiation Oncology Physics: A Handbook for Teachers and Students - 14.2 Slide 5 14.3 CELL CYCLE AND CELL DEATH Cell proliferation cycle is defined by two time periods: • Mitosis M, where division takes place. • The period of DNA synthesis S. S and M portions of the cell cycle are separated by two periods (gaps) G1 and G2 when, respectively • DNA has not yet been synthesized. • Has been synthesized but other metabolic processes are taking place. IAEA Radiation Oncology Physics: A Handbook for Teachers and Students - 14.3 Slide 1 14.3 CELL CYCLE AND CELL DEATH Time between successive divisions (mitoses) is called cell cycle time. Cell cycle time for mammalian cells is of the order of 10 – 20 hours: • S phase is usually in the range of 6 – 8 hours. • M phase is less than 1 hour. • G2 is in the range of 2 – 4 hours. • G1 is in the range of 1 – 8 hours. Stages of the mitotic cell cycle M = mitosis S = DNA synthesis G1 and G2 = gaps IAEA Radiation Oncology Physics: A Handbook for Teachers and Students - 14.3 Slide 2 14.3 CELL CYCLE AND CELL DEATH Cell cycle time for stem cells in certain tissues is up to 10 days. In general, cells are most radio-sensitive in the M and G2 phases, and most radio-resistant in the late S phase. Cell cycle time of malignant cells is shorter than that of some normal tissue cells, but during regeneration after injury normal cells can proliferate faster. IAEA Radiation Oncology Physics: A Handbook for Teachers and Students - 14.3 Slide 3 14.3 CELL CYCLE AND CELL DEATH Cell death of non-proliferating (static) cells is defined as the loss of a specific function. Cell death for stem cells and other cells capable of many divisions is defined as the loss of reproductive integrity (reproductive death). IAEA Radiation Oncology Physics: A Handbook for Teachers and Students - 14.3 Slide 4 14.4 IRRADIATION OF CELLS When cells are exposed to ionizing radiation: • First, the standard physical effects between radiation and the atoms or molecules of the cells occur. • Possible biological damage to cell functions follows. Biological effects of radiation result mainly from damage to the DNA; however, there are also other sites within the cell that, when damaged, may lead to cell death. IAEA Radiation Oncology Physics: A Handbook for Teachers and Students - 14.4 Slide 1 14.4 IRRADIATION OF CELLS Surviving cell that maintains its reproductive integrity and proliferates almost indefinitely into a large number of progeny is said to be clonogenic. Capability of a single cell to grow into a large colony shows that the cell has retained its reproductive integrity. In general, to destroy cell function in non-proliferating cells a typical dose of 100 Gy is required, while to destroy proliferative cell capacity requires typically only 2 Gy. IAEA Radiation Oncology Physics: A Handbook for Teachers and Students - 14.4 Slide 2 14.4 IRRADIATION OF CELLS Sensitive component for radiation-induced cell killing rests in the cell nucleus and not in the cytoplasm. When directly ionizing radiation is absorbed in biological material, the damage to the cell may occur in one of two mechanisms: • Direct • Indirect IAEA Radiation Oncology Physics: A Handbook for Teachers and Students - 14.4 Slide 3 14.4 IRRADIATION OF CELLS 14.4.1 Direct action in cell damage by radiation In direct action the radiation interacts directly with the critical target in the cell.
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