Chapter 33 Radiobiology

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Chapter 33 Radiobiology

• Radiobiology is the study of the effects of
  ionizing radiation on biologic tissues.
• The ultimate goal of research is to develop
  dose-response relationships so the effects of
  planned doses can be predicted and the response
  to accidental exposure better managed.

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Radiobiology

• The effect of x-ray radiation on humans is the
  result of interactions at the atomic level.
• The forms of interaction
• Ionization of the tissue
• Excitation of orbital electrons
• Results is the disposition of energy in the
  tissues.

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Effects of Ionizing Radiation Exposure

• When the atom is ionized, its chemical bonding
  properties change.
• If the atom is part of a large molecule, it
  result in breakage of the the molecule or
  relocation of the atom within the molecule.
• The abnormal molecule may function improperly or
  die.

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Effects of Ionizing Radiation Exposure

• This may result in serious impairment of the
  cell function or cell death.
• This process can be reversible if the atom
  attracts a free electron.
• Molecules can be mended by repair enzymes.
• Cells and tissue can regenerate.

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Types of Radiation Response

• If the response to radiation happens in minutes
  or days it is referred to as early effects of
  radiation.
• If the responds is not observed for six months or
  more, it is termed to be late effects of
  radiation.

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Early Responses to Radiation in Humans

• Acute radiation syndrome
• Hematological Syndrome
• Gastrointestinal Syndrome
• Central Nervous System Syndrome
• Local tissue damage
• Skin
• Gonads
• Extremities

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Early Responses to Radiation in Humans

• Hematological depression
• Cytogenesis damage

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Late Responses to Radiation in Humans

• Leukemia
• Other malignant disease
• Bone Cancer
• Lung Cancer
• Thyroid Cancer
• Breast Cancer

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Late Responses to Radiation in Humans

• Local tissue damage
• Skin
• Gonads
• Eyes
• Shortened life span
• Genetic damage
• Cytogenesis damage
• Doubling dose
• Genetically significant dose

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Effects of Fetal Irradiation in Humans

• Prenatal death
• Neonatal death
• Congenital malformations
• Childhood malignancy
• Diminished growth and development.

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Effects of Irradiation in Humans

• Most of the observed effects have been observed
  after rather large doses.
• As operators of x-ray machines, we must assume
  that even small doses can be harmful.

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Human Populations in Which Radiation Effects have
Been Observed

• Population
• American radiologists
• Atomic bomb survivors
• Radiation accident victims
• Marshall Islanders
• Uranium miners
• Radium watch dial painters
• Patients treated with 131I
• Children treated for enlarged thymus
• Irradiation in utero
• Volunteer convicts

• Effect
• Leukemia, reduced life span
• Malignant disease
• Acute lethality
• Thyroid cancer
• Lung cancer
• Bone cancer
• Thyroid cancer
• Thyroid cancer
• Childhood malignancy
• Fertility impairment

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Sequence of Events after ExposureRadiation
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Radiation Interaction at the Atomic Level

• At the most basic level, the human body is made
  up of atoms.
• Radiation interacts at this level.
• The atomic composition of the body determines the
  character and degree of the radiation
  interaction.
• The molecular and tissue composition defines the
  nature of the radiation response.

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Radiation Interaction at the Atomic Level

• Over 85 of the body is composed of hydrogen and
  oxygen.
• Radiation interaction at the atomic level results
  in molecular change, and this in turn can produce
  a cell deficient in normal growth and metabolism.

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Molecular Composition

• There are five principle types of molecules in
  the body
• Four are macromolecules , sometimes consisting of
  hundreds of thousands of atoms.
• Proteins
• Lipids (fats)
• Carbohydrates (sugars and starches)
• Nucleic Acids (DNA)
• DNA is the most critical radiosensitive
  molecule.

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Molecular Composition

• 80 Water
• 15 Protein
• 2 Lipids
• 1 Carbohydrates
• 1 Nucleic Acid (DNA)
• 1 Other

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Water 80

• Water is the most abundant and simplest molecule
  in the body.
• It delivers energy to the target molecule and
  thereby contributing to the radiation affects.
• Water also helps control temperature
• Water provides form and shape to the cell.

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Protein 15

• Proteins are long chains of macromolecules
  consisting of amino acids connected by peptide
  bonds.
• There are 22 amino acids used in protein
  synthesis or the metabolic production of protein.
• The linear sequence determines the function of
  the protein.

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Uses of Protein

• Proteins provide structure and support. Muscles
  are very high in protein content.
• Proteins function as enzymes, hormones or
  antibodies.

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Enzymes

• Enzymes are molecules that allow biochemical
  reactions to continue without being part of the
  reaction.
• They function as a catalyst for the chemical
  reaction.

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Hormones Antibodies

• Hormones exercise regulatory control over some
  body functions such as
• Growth
• Development
• Metabolic Rate
• Hormones produced by the endocrine glands.
• Antibodies provide defense from disease.

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Lipids 2

• Lipids are organic macromolecules composed of
  carbon, hydrogen and oxygen.
• Lipids are composed of glycerol and fatty acids.
• Lipids are present in all tissues and are the
  structural component of cell membranes.

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Lipids

• Lipids tend to concentrate just under the skin.
• Lipids provide heat insulation.
• Lipids serve as fuel or energy stores for the
  body. It is more difficult to extract the energy
  compared to carbohydrates resulting in obesity.

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Carbohydrates 1

• Like lipids are composed of carbon, hydrogen and
  oxygen but the structure is different.
• The structural difference determines the
  contribution of the carbohydrate molecule to
  biochemistry.
• Some carbohydrates provide shape and stability
  to the cell.
• Primary function is to provide fuel for cell
  metabolism.

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Nucleic Acids 1

• There are two principle nucleic acids of
  importance to human metabolism.
• DNA and RNA
• DNA located in the nucleus of the cell serves as
  the control molecule for cell function. DNA
  contains all of the heredity information for the
  cell or the entire organism if it is a germ cell.

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Nucleic Acids 1

• RNA is found primarily in the cytoplasm but is
  also found in the nucleus. There are two types of
  RNA.
• Messenger RNA (mRNA)
• Transfer RNA (tRNA)
• RNA is involved in growth and development of the
  cell through biochemical pathways, notably
  through protein synthesis.

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Nucleic Acids 1

• DNA is the principle radiation sensitive molecule.

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Human Cell Composition

• Two major structure of the cell are
• Nucleus containing the DNA
• Cytoplasm makes up the bulk of the cell and
  contains all of the other cell structures.
• Endoplasmic reticulum is a series of channels
  that allows the nucleus to communicate with the
  cytoplasm.

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Human Cell Composition

• Mitochondria are large bean shaped structures
  that digest macromolecules to produce energy for
  the cell.
• Ribosome are sites of protein synthesis and are
  essential to normal cell function.

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Human Cell Composition

• Lysosomes contain enzymes capable of digesting
  cellular fragments and in some cases the cell
  itself.
• Lysosomes are helpful in the control of
  intracellular contaminates.
• All structures are surrounded by membranes of
  lipid proteins.

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Cellular Irradiation

• When the critical macromolecular cellular
  components are irradiated, a dose of about 1
  Mrad or 10 kGy is required to produce a
  measurable change in the physical characteristics
  of the cell.

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Cellular Irradiation

• When such a molecule is incorporated into the
  apparatus of a living cell, only a few rad are
  necessary to produce a measurable response.
• Some single cell organisms require massive
  exposure to produce a lethal dose.

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Cellular Irradiation

• Human cells can be killed with a dose less than
  100 rad (1Gy).
• The nucleus is much more sensitive than the
  cytoplasm to radiation exposure.
• Interference with any phase of protein synthesis
  could result in cell damage particularly DNA.

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Cell Proliferation

• Cell proliferation is the act of a single cell
  or group of cells reproducing and multiplying in
  number.
• It takes many thousands of rads to disrupt
  macromolecules, single ionizing events to
  sensitive cell sites can disrupt proliferation.

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Types of Cell Proliferation

• Genetic cells (oogonium of the female and
  spermatogonium of the male) undergo meiosis.
• Somatic cells undergo mitosis.

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Cell Cycle

• Cell biologist identify four phases of the cell
  cycle
• Mitosis
• G1 first growth
• S synthesis
• G2 second growth
• DNA synthesis is in the S phase

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Phases of Mitosis

• A-Interphase has the DNA forming chromosomes.
• B-Prophase the nucleus swells and the DNA takes a
  more structural form.
• C-Metaphase the chromosomes appear and line up
  along the equator of the nucleus. During
  metaphase, mitosis can be stopped and damage
  analyzed.

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Phases of Mitosis

• F- Anaphase each chromosomes splits to form a
  centromere and two chromatids connected by a
  fiber to the poles of the nucleus. These poles
  are called spindles and the fiber called spindle
  fibers.
• The number of chromosomes have been reduced by
  half.

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Phases of Mitosis

• The chromosomes slowly migrate toward the
  spindle.
• E- Telophase is characterized by the
  disappearance of the chromosomes into a mass of
  DNA and closing off of the nucleus like a pair of
  dumbbells into two nuclei. The cytoplasm divides
  equally into two cells and interphase begins.
• D- Interphase starts again.

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Meiosis

• Genetic cell division is called meiosis.
• Genetic cells begin with 46 chromosomes like
  somatic cells.
• During the first division, the daughter,
  replicated the DNA with 46 chromosomes.

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Meiosis

• During the second meiosis, there is no S phase so
  the DNA does not replicate. Granddaughter cells
  have 23 chromosomes.
• There is some exchange of chromosomal or
  crossover resulting in the genetic constitution
  and changes in inheritable traits.

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Human development

• During the development and maturation of a human
  from the two united genetic cells, a number of
  cell types evolve.
• Collections of cells of similar structure and
  function form tissue.
• Tissue forms organs and organs form organ systems.

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Principle Organ Systems

• Nervous System
• Digestive System
• Endocrine System
• Respiratory System
• Reproductive System
• Cells of organ systems are identified by their
  rate of proliferation and stage of development.

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Cell development

• Underdiffentriated cell, precursor cells or stem
  cells are immature cells. They are more sensitive
  cells to radiation than mature cells.
• The sensitivity of cells to radiation is
  determined to some degree by its state of
  maturity and its functional role.

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Cell development

• The tissues and organs of the body contain both
  stem and mature cells.
• There are several types of tissue classified by
  their structural or functional appearance. These
  features influence the degree of radiosensitivity
  of the tissue.

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End of lecture