Week 8 a 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.
 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.
 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
may result in breakage of the the molecule
or relocation of the atom within the
molecule.
• The abnormal molecule may function
improperly or die.
 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.
 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.
 Early Responses to Radiation in
Humans
• Acute radiation syndrome
– Hematological Syndrome
– Gastrointestinal Syndrome
– Central Nervous System Syndrome
• Local tissue damage
– Skin
– Gonads
– Extremities
 Early Responses to Radiation in
Humans
• Hematological depression
• Cytogenesis damage
 Late Responses to Radiation in
Humans
• Leukemia
• Other malignant disease
– Bone Cancer
– Lung Cancer
– Thyroid Cancer
– Breast Cancer
 Late Responses to Radiation in
Humans
• Local tissue damage
– Skin
– Gonads
– Eyes
• Shortened life span
• Genetic damage
– Cytogenesis damage
– Doubling dose
– Genetically significant dose
 Effects of Fetal Irradiation in
Humans
• Prenatal death
• Neonatal death
• Congenital malformations
• Childhood malignancy
• Diminished growth and development.
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.
 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
Sequence of Events after Exposure
Radiation
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.
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.
 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.
 Molecular Composition
• 80% Water
• 15% Protein
• 2% Lipids
• 1% Carbohydrates
• 1% Nucleic Acid (DNA)
• 1% Other
 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.
 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.
 Uses of Protein
• Proteins provide structure and support.
Muscles are very high in protein content.
• Proteins function as enzymes, hormones
or antibodies.
 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.
 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.
 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.
 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.
 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.
 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.
 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.
 Nucleic Acids 1%
– DNA is the principle radiation sensitive
molecule.
 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.
 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.
 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.
 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.
 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.
 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.
 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.
 Types of Cell Proliferation
• Genetic cells (oogonium of the female
and spermatogonium of the male) undergo
meiosis.
• Somatic cells undergo mitosis.
 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
 Phases of Mitosis
• Interphase has the DNA forming
chromosomes.
• Prophase the nucleus swells and the DNA
takes a more structural form.
• Metaphase the chromosomes appear and
line up along the equator of the nucleus.
During metaphase, mitosis can be stopped
and damage analyzed.
 Phases of Mitosis
• 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.
 Phases of Mitosis
• The chromosomes slowly migrate toward
the spindle.
• 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.
 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.
 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.
 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.
 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.
 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.
 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.
 End of Lecture

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