Transcript Slide 1

Cell Biology
Radiobiology is the study
of the effects of ionizing
radiation on biologic
tissue
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.
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.
Human Populations in Whom Radiation Effects Have
Been Observed:
Population
Effect
American radiologists
Leukemia, reduced life span
Atomic bomb survivors
Malignant disease
Radiation accident victims (e.g.,
Chernobyl)
Acute lethality
Marshall Islanders
Thyroid cancer
Uranium miners
Lung cancer
Radium watch-dial painters
Bone cancer
Patients treated with 131I
Thyroid cancer
Children treated for enlarged
thymus
Thyroid cancer
Children of Belarus (downwind
from Chernobyl)
Thyroid cancer
Patients with ankylosing
spondylitis
Leukemia
Patients who underwent
Thorotrast studies
Liver cancer
Irradiation in utero
Childhood malignancy
Volunteer convicts
Fertility impairment
Cyclotron workers
Cataracts
Five principal types of molecules are found in the
body . Four of these molecules—proteins, lipids
(fats), carbohydrates (sugars and starches), and
nucleic acids—are macromolecules.
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
molecules—a nucleic acid concentrated in the
nucleus of a cell (DNA)—is considered to be
the most critical and radiosensitive target
molecule.
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
Molecular Composition of the Body
• 80% water
• 15% protein
• 2% lipids
• 1% carbohydrates
• 1% nucleic acid
• 1% other
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
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.
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
Carbohydrates
Carbohydrates, similar to lipids, are composed
solely of carbon, hydrogen, and oxygen, but
their structure is different
Carbohydrates also are called saccharides.
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
DNA
is the radiation-sensitive
target molecule.
DNA consists of a backbone composed of alternating
segments of deoxyribose (a sugar) and phosphate
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 sugar–phosphate 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 sugar–phosphate molecules, and the
rungs of the ladder consist of bases joined together
by hydrogen bonds.
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.
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.
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.
http://www.cellsalive.com/cells/cell_mo
del.htm
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.
When the critical macromolecular cellular
components are irradiated by themselves, a
dose of approximately 1 Mrad (10 kGyt) is
required to produce a measurable change in
any physical characteristic of the molecule
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
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
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
http://www.cellsalive.com/mitosis.htm
http://www.cellsalive.com/meiosis.htm
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.
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.
The sensitivity of the cell to radiation is determined
somewhat by its state of maturity and its functional
role
Stem cells are more sensitive to radiation than
mature cells
Radiosensitivity
Cell Type
High
Lymphocytes
Spermatogonia
Erythroblasts
Intestinal crypt cells
Intermediate
Endothelial cells
Osteoblasts
Spermatids
Fibroblasts
Low
Muscle cells
Nerve cells
High: 200 to 1000 rad (2
Lymphoid tissue
to 10 Gyt)
Bone marrow
Gonads
Intermediate: 1000 to
5000 rad (10 to 50 Gyt)
Low: >5000 rad (>50
Gyt)
Atrophy
Hypoplasia
Atrophy
Skin
Erythema
Gastrointestinal tract
Ulcer
Cornea
Growing bone
Kidney
Liver
Thyroid
Cataract
Growth arrest
Nephrosclerosis
Ascites
Atrophy
Muscle
Fibrosis
Brain
Spinal
Necrosis
Transection