Chapter 14: Basic Radiobiology - IAEA NA

Chapter 14: Basic RadiobiologySet of 88 slides based on the chapter authored byN. Suntharalingam, E.B. Podgorsak, J.H. Hendryof the IAEA publication (ISBN 92-0-107304-6):Radiation Oncology Physics:A Handbook for Teachers and StudentsObjective:To familiarize the student with the basic principles of radiobiology.Slide set prepared in 2006by E.B. Podgorsak (Montreal, McGill University)Comments to S. Vatnitsky:dosimetry@iaea.orgVersion 2012IAEAInternational Atomic Energy Agency

CHAPTER .10.14.11.14.12.14.13.TABLE OF CONTENTSIntroductionClassification of radiations in radiobiologyCell cycle and cell deathIrradiation of cellsType of radiation damageCell survival curvesDose response curvesMeasurement of radiation damage in tissueNormal and tumour cells: Therapeutic ratioOxygen effectRelative biological effectivenessDose rate and fractionationRadioprotectors and radiosensitizersIAEARadiation Oncology Physics: A Handbook for Teachers and Students - 14.

14.1 INTRODUCTION Radiobiology is a branch of science which combines thebasic principles of physics and biology and is concernedwith the action of ionizing radiation on biological tissuesand living organisms. Study of basic radiobiological mechanisms deals withbiological effects produced by energy absorption in smallvolumes corresponding to single cells or parts of cells.IAEARadiation Oncology Physics: A Handbook for Teachers and Students - 14.1 Slide 1

14.1 INTRODUCTION All living entities are made up of protoplasm, whichconsists if inorganic and organic compounds dissolved orsuspended in water. The smallest unit of protoplasm capable of independentexistence is the cell, the basic microscopic unit of all livingorganisms.IAEARadiation Oncology Physics: A Handbook for Teachers and Students - 14.1 Slide 2

14.1 INTRODUCTION Group of cells that together perform one or morefunctions is referred to as tissue. Group of tissues that together perform one or morefunctions is called an organ. Group of organs that perform one or more functions is anorgan system or an organism.IAEARadiation 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 andthe nucleus: Cytoplasm supports all metabolic functions within a cell. Nucleus contains the genetic information (DNA).IAEARadiation 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 humancells are called somatic cells. Cells propagate through division: Division of somatic cells is called mitosis and results in twogenetically identical daughter cells. Division of germ cells is called meiosis and involves two fissionsof the nucleus giving rise to four sex cells, each possessing halfthe number of chromosomes of the original germ cell.IAEARadiation Oncology Physics: A Handbook for Teachers and Students - 14.1 Slide 5

14.1 INTRODUCTION When a somatic cell divides, two cells are produced, eachcarrying a chromosome complement identical to that ofthe original cell. New cells themselves may undergo further division, andthe process continues producing a large number ofprogeny.IAEARadiation Oncology Physics: A Handbook for Teachers and Students - 14.1 Slide 6

14.1 INTRODUCTION Chromosome is a microscopic, threadlike part of a cell thatcarries hereditary information in the form of genes. Every species has a characteristic number of chromosomes;humans have 23 pairs (22 pairs are non-sex chromosomesand 1 pair is sex chromosome). Gene is a unit of heredity that occupies a fixed position on achromosome.IAEARadiation 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 adifferentiated cell population. Transit cells, which are cells in movement to another population. Mature cells, which are fully differentiated and do not exhibitmitotic activity.IAEARadiation 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.IAEARadiation 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 energytransfer (LET) is used for defining the quality of anionizing radiation beam. In contrast to the stopping power, which focuses attentionon the energy loss by a charged particle moving througha medium, LET focuses attention on the linear rate ofenergy absorption by the absorbing medium as thecharged particle traverses the medium.IAEARadiation 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 quotientdE /d where dE is the average energy locallyimparted to the medium by a charged particle ofspecified energy in traversing a distance of d .”IAEARadiation 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 unitof MeV/cm, the unit reserved for the LET is keV/ m . Energy average is obtained by dividing the particle trackinto equal energy increments and averaging the length oftrack over which these energy increments are deposited.IAEARadiation 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 250 kVp X rays Cobalt-60 rays 3 MeV X rays 1 MeV electronsLET (keV/ m)20.30.30.25 LET values for other, less common radiations are:RadiationLET (keV/ m) 14 MeV neutrons12 Heavy charged particles100 – 200 1 keV electrons12.3 10 keV electrons2.3IAEARadiation 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 twoperiods (gaps) G1 and G2 when, respectively DNA has not yet been synthesized. Has been synthesized but other metabolic processes are takingplace.IAEARadiation 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 calledcell cycle time. Cell cycle time for mammalian cells is of the order of10 – 20 hours: S phase is usually inthe 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 cycleM mitosisS DNA synthesisG1 and G2 gapsIAEARadiation 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 10days. In general, cells are most radio-sensitive in the M and G2phases, and most radio-resistant in the late S phase. Cell cycle time of malignant cells is shorter than that ofsome normal tissue cells, but during regeneration afterinjury normal cells can proliferate faster.IAEARadiation 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 asthe loss of a specific function. Cell death for stem cells and other cells capable of manydivisions is defined as the loss of reproductive integrity(reproductive death).IAEARadiation 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 theatoms or molecules of the cells occur. Possible biological damage to cell functions follows. Biological effects of radiation result mainly from damageto the DNA; however, there are also other sites within thecell that, when damaged, may lead to cell death.IAEARadiation Oncology Physics: A Handbook for Teachers and Students - 14.4 Slide 1

14.4 IRRADIATION OF CELLS Surviving cell that maintains its reproductive integrityand proliferates almost indefinitely into a large number ofprogeny is said to be clonogenic. Capability of a single cell to grow into a large colonyshows that the cell has retained its reproductive integrity. In general, to destroy cell function in non-proliferatingcells a typical dose of 100 Gy is required, while todestroy proliferative cell capacity requires typically only2 Gy.IAEARadiation Oncology Physics: A Handbook for Teachers and Students - 14.4 Slide 2

14.4 IRRADIATION OF CELLS Sensitive component for radiation-induced cell killing restsin the cell nucleus and not in the cytoplasm. When directly ionizing radiation is absorbed in biologicalmaterial, the damage to the cell may occur in one of twomechanisms: Direct IndirectIAEARadiation Oncology Physics: A Handbook for Teachers and Students - 14.4 Slide 3

14.4 IRRADIATION OF CELLS14.4.1 Direct action in cell damage by radiation In direct action the radiation interacts directly with thecritical target in the cell. In direct action the atoms of the target itself may be ionizedor excited through Coulomb interactions, leading to thechain of physical and chemical events that eventuallyproduce the biological damage.IAEARadiation Oncology Physics: A Handbook for Teachers and Students - 14.4.1 Slide 1

14.4 IRRADIATION OF CELLS14.4.1 Direct action in cell damage by radiation Direct action is the dominant process in the interaction ofhigh LET particles such as neutrons or alpha particleswith biological material. In direct action caused by x-ray or gamma ray photons,the photon interaction with an atom in the cell produces acharged particle (electron or positron) whichsubsequently interacts with the DNA directly.IAEARadiation Oncology Physics: A Handbook for Teachers and Students - 14.4.1 Slide 2

14.4 IRRADIATION OF CELLS14.4.2 Indirect action in cell damage by radiation In indirect action the radiation interacts with othermolecules and atoms (mainly water, since about 80% of acell is composed of water) within the cell to produce freeradicals, which can, through diffusion in the cell, damagethe critical target within the cell. Indirect action can be modified by chemical sensitizers orradiation protectors.IAEARadiation Oncology Physics: A Handbook for Teachers and Students - 14.4.2 Slide 1

14.4 IRRADIATION OF CELLS14.4.2 Indirect action in cell damage by radiation Basic radiochemical reactions that may occur in watermolecules disrupted by passage of an ionizing particle areas follows: 1. 2. 3.IAEAh H2O H2O e H2O eaqH2O OH H h H2O H2O H OH Radiation Oncology Physics: A Handbook for Teachers and Students - 14.4.2 Slide 2

14.4 IRRADIATION OF CELLS14.4.2 Indirect action in cell damage by radiation Highly reactive species produced in water through the, OH and H .radiochemical reactions are: eaq These reactive species bring about the indirect radiationdamage to biological system by reacting and damagingthe molecules in cells.IAEARadiation Oncology Physics: A Handbook for Teachers and Students - 14.4.2 Slide 3