Basic Radiation Biology Concepts PDF

BASIC RADIATION BIOLOGY CONCEPTS 1  Radiobiology 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....

BASIC RADIATION BIOLOGY CONCEPTS 1  Radiobiology 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 2  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. 3  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. 4  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). 5  Human cells are: Somatic cells 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. 6  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. 7  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. 8  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. 9 Stem Cells 10  Stem Cell – Definition A cell that has the ability to continuously divide and differentiate (develop) into various other kind(s) of cells/tissues 11  What is a stem cell? stem cell SELF-RENEWAL DIFFERENTIATION (copying) (specializing) specialized cell stem cell e.g. muscle cell, nerve cell 12  Stem cells are different from other cells of the body because stem cells can both: Self-renew: Make copies of themselves Differentiate: Make other types of cells – specialized cells of the body. 13  ‘Specialized’ or ‘differentiated’ cells play particular roles in the body, e.g. blood cells, nerve cells, muscle cells. Specialized cells cannot divide to make copies of themselves. This makes stem cells very important. The body needs stem cells to replace specialized cells that die, are damaged or get used up. 14 Why is Stem Cell Research So Important to All of Us? Stem cells can replace diseased or damaged cells Stem cells allow us to study development and genetics Stem cells can be used to test different substances (drugs and chemicals) 15  The law of Bergonié and Tribondeau A fundamental law of radiation biology that states that the radio-sensitivity of a tissue is increased the greater the number of undifferentiated cells in the tissue, the greater the mitotic activity, and the greater the length of time that they are actively proliferating. 16  The law of Bergonié and Tribondeau Radio-sensitivity of living tissues varies with maturation & metabolism; 1. Stem cells are radiosensitive. More mature cells are more resistant 2. Younger tissues are more radiosensitive 3. Tissues with high metabolic activity are highly radiosensitive 4. High proliferation and growth rate, high radio- sensitivty 17 1. Radio-sensitizer molecules 2. Radio-protector molecules (radio-resistant) 18  The law of Bergonié and Tribondeau They respond by exhibiting some effect from radiation exposure that causes cell injury or death. Cells that are mature, differentiated and not actively dividing (i.e., neurons) are more radio-resistant. A cell that is radiosensitive would be more inclined to die after exposure to ionizing radiation than a radioresistant cell. more or less radio-responsive Cells undergoing active mitosis are more likely to have an effect from ionizing radiation, and stem cells (bone marrow, stomach mucosa, germ layer of the skin) are much more radiosensitive than neurons, which either never replicate or do so very slowly. 19  Experiments in fruit flies and mice have shown that the effects of ionizing radiation can cause mutations in progeny, but these mutations are not specific to radiation. Such mutations are similar to ones that have already been found to occur spontaneously in nature. Furthermore, the experiments showed that the effects of ionizing radiation depend on total dose and exposure rate. A large dose given in a short amount of time is more damaging than the same dose given over a longer period of time. 20  The interaction of radiation with cells is a probability function. Because cellular repair usually takes place, permanent damage will not necessarily result from an interaction of ionizing radiation with living tissue. Energy deposition to a cell occurs very quickly, in some 10-18 s. In addition, there is no unique cellular damage associated with radiation. Any damage to a cell due to radiation exposure may also happen due to chemical, heat, or physical damage. 21  After radiation exposure to a cell, there is a latent period before any observable response. The latent period could be decades for low radiation doses, but only minutes or hours for high radiation exposure. These basic generalizations form the foundation on which radiation biology is based. 22  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 23  RADIATION INTERACTIONS WITH HUMAN CELLS What happens in a cell when ionizing radiation interacts with it? There are really only 2 possibilities: direct interaction or indirect interaction in a cell. 24  Direct Interaction In direct interaction, a cell’s macromolecules (proteins or DNA) are hit by the ionizing radiation, which affects the cell as a whole, either killing the cell or mutating the DNA. There are many target and cell survival studies that show that it is harder to permanently destroy or break double-stranded DNA than single-stranded DNA. Although humans have 23 pairs of double-stranded chromosomes, some cells react as if they contain single- stranded, nonpaired chromosomes and are more radiosensitive. 25  Many different types of direct hits can occur, and the type of damage that occurs determines whether or not the cell can repair itself. Generally, if a direct hit causes a complete break in the DNA or some other permanent damage, the cell dies immediately or will die eventually. However, humans have an abundance of cells and somatic cellular reproduction (mitosis) is always occurring to replace cells that die. 26  Therefore, it is only when this system of replacing cells falters that radiation effects are seen. This occurs at higher doses of radiation. Actively dividing cells are more radiosensitive than non dividing cells. 27 There are 4 phases of mitosis: M Phase, in which cells divide in 2; G1 Phase (gap one), in which cells prepare for DNA replication; S Phase, in which DNA doubles by replication; G2 Phase (gap two), in which cells prepare for mitosis. Of these, M phase, in which the chromosomes are condensed and paired, is the most radiosensitive. 28 29