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Cell Biology Slide 2 Radiobiology is the study of the effects of ionizing radiation on biologic tissue Slide 3 At its most basic level, the human body is composed of atoms; radiation interacts at the atomic level. The atomic composition of the body determines the character and degree of the radiation interaction that occurs. The molecular and tissue composition defines the nature of the radiation response. Slide 4 Radiation interaction at the atomic level results in molecular change, which can produce a cell that is deficient in terms of normal growth and metabolism. Slide 5 Human Populations in Whom Radiation Effects Have Been Observed: PopulationEffect American radiologistsLeukemia, reduced life span Atomic bomb survivorsMalignant disease Radiation accident victims (e.g., Chernobyl) Acute lethality Marshall IslandersThyroid cancer Uranium minersLung cancer Radium watch-dial paintersBone cancer Patients treated with 131 IThyroid cancer Children treated for enlarged thymus Thyroid cancer Slide 6 Children of Belarus (downwind from Chernobyl) Thyroid cancer Patients with ankylosing spondylitis Leukemia Patients who underwent Thorotrast studies Liver cancer Irradiation in uteroChildhood malignancy Volunteer convictsFertility impairment Cyclotron workersCataracts Slide 7 Five principal types of molecules are found in the body. Four of these moleculesproteins, lipids (fats), carbohydrates (sugars and starches), and nucleic acidsare macromolecules. Slide 8 Macromolecules are very large molecules that sometimes consist of hundreds of thousands of atoms. Proteins, lipids, and carbohydrates are the principal classes of organic molecules. An organic molecule is life-supporting and contains carbon. One of the rarest moleculesa nucleic acid concentrated in the nucleus of a cell (DNA)is considered to be the most critical and radiosensitive target molecule. Slide 9 Atomic Composition of the Body 60.0% hydrogen 25.7% oxygen 10.7% carbon 2.4% nitrogen 0.2% calcium 0.1% phosphorus 0.1% sulfur 0.8% trace elements Slide 10 Molecular Composition of the Body 80% water 15% protein 2% lipids 1% carbohydrates 1% nucleic acid 1% other Slide 11 Water is the most abundant molecule in the body, and it is the simplest. Water, however, plays a particularly important role in delivering energy to the target molecule, thereby contributing to radiation effects. In addition to water and the macromolecules, some trace elements and inorganic salts are essential for proper metabolism Slide 12 Proteins Approximately 15% of the molecular composition of the body is protein. Proteins are long-chain macromolecules that consist of a linear sequence of amino acids connected by peptide bonds. Twenty-two amino acids are used in protein synthesis, the metabolic production of proteins. The linear sequence, or arrangement, of these amino acids determines the precise function of the protein molecule. Slide 13 Lipids are present in all tissues of the body and are the structural components of cell membranes. Lipids often are concentrated just under the skin and serve as a thermal insulator from the environment Slide 14 Carbohydrates Carbohydrates, similar to lipids, are composed solely of carbon, hydrogen, and oxygen, but their structure is different Carbohydrates also are called saccharides. Slide 15 Nucleic Acids Two principal nucleic acids are important to human metabolism: deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Located principally in the nucleus of the cell, DNA serves as the command or control molecule for cell function. DNA contains all the hereditary information that represents a cell and, of course, if the cell is a germ cell, all the hereditary information of the whole individual Slide 16 DNA is the radiation-sensitive target molecule. Slide 17 DNA consists of a backbone composed of alternating segments of deoxyribose (a sugar) and phosphate Slide 18 Attached to each deoxyribose molecule is one of four different nitrogen-containing or nitrogenous organic bases: adenine, guanine, thymine, or cytosine. Adenine and guanine are purines; thymine and cytosine are pyrimidines. The base sugarphosphate combination is called a nucleotide, and the nucleotides are strung together in one long-chain macromolecule. Human DNA exists as two of these long chains attached together in ladder fashion The side rails of the ladder are the alternating sugarphosphate molecules, and the rungs of the ladder consist of bases joined together by hydrogen bonds. Slide 19 To complete the picture, the ladder is twisted about an imaginary axis such as a spring. This produces a molecule with the double-helix configuration The sequence of base bonding is limited to adenines bonded to thymines and cytosines bonded to guanines. Slide 20 Structurally, RNA resembles DNA. In RNA, the sugar component is ribose rather than deoxyribose, and uracil replaces thymine as a base component. In contrast, RNA forms a single spiral, not a double helix. Slide 21 Slide 22 THE HUMAN CELL The two major structures of the cell are the nucleus and the cytoplasm. The principal molecular component of the nucleus is DNA, the genetic material of the cell. The nucleus also contains some RNA, protein, and water. Most of the RNA is contained in a rounded structure, the nucleolus. The nucleolus often is attached to the nuclear membrane, a double-walled structure that at some locations is connected to the endoplasmic reticulum. This connection by its nature controls the passage of molecules, particularly RNA, from nucleus to cytoplasm. Slide 23 Slide 24 http://www.cellsalive.com/cells/cell_mo del.htm Slide 25 The cytoplasm makes up the bulk of the cell and contains great quantities of all molecular components except DNA. A number of intracellular structures are found in the cytoplasm. The endoplasmic reticulum is a channel or a series of channels that allows the nucleus to communicate with the cytoplasm. Slide 26 When the critical macromolecular cellular components are irradiated by themselves, a dose of approximately 1 Mrad (10 kGy t ) is required to produce a measurable change in any physical characteristic of the molecule Slide 27 Although many thousands of rad (many gray) are necessary to produce physically measurable disruption of macromolecules in vitro, single ionizing events at a particularly sensitive site of a critical target molecule are thought to be capable of disrupting cell proliferation Slide 28 Cell proliferation is the act of a single cell or group of cells to reproduce and multiply in number. The human body consists of two general types of cells: somatic cells and genetic cells. The genetic cells include the oogonium of the female and the spermatogonium of the male. All other cells of the body are somatic cells. When somatic cells proliferate or divide, they undergo mitosis. Genetic cells undergo meiosis Slide 29 The cell biologist and the geneticist view the cell cycle differently Each cycle includes the various states of cell growth, development, and division. The geneticist considers only two phases of the cell cycle: mitosis (M) and interphase Slide 30 http://www.cellsalive.com/mitosis.htm Slide 31 http://www.cellsalive.com/meiosis.htm Slide 32 At metaphase, the chromosomes appear and are lined up along the equator of the nucleus. It is during metaphase that mitosis can be stopped and chromosomes can be studied carefully under the microscope. Radiation-induced chromosome damage is analyzed during metaphase. Slide 33 The cells of a tissue system are identified by their rate of proliferation and their stage of development. Immature cells are called undifferentiated cells, precursor cells, or stem cells. As a cell matures through growth and proliferation, it can pass through various stages of differentiation into a fully functional and mature cell. Slide 34 Stem cells are more sensitive to radiation than mature cells The sensitivity of the cell to radiation is determined somewhat by its state of maturity and its functional role Slide 35 RadiosensitivityCell Type HighLymphocytes Spermatogonia Erythroblasts Intestinal crypt cells IntermediateEndothelial cells Osteoblasts Spermatids Fibroblasts LowMuscle cells Nerve cells Slide 36 High: 200 to 1000 rad (2 to 10 Gy t ) Lymphoid tissueAtrophy Bone marrowHypoplasia GonadsAtrophy Intermediate: 1000 to 5000 rad (10 to 50 Gy t ) SkinErythema Gastrointestinal tractUlcer CorneaCataract Growing boneGrowth arrest KidneyNephrosclerosis LiverAscites ThyroidAtrophy Low: >5000 rad (>50 Gy t ) MuscleFibrosis BrainNecrosis SpinalTransection