Transcript Cell Biology

Cell Biology
HUMAN RADIATION RESPONSE
The effect of x-rays on humans is the result of interactions at the
atomic level These atomic interactions take the form of ionization or
excitation of orbital electrons and result in the deposition of energy in
tissue.
Deposited energy can produce a molecular change, the
consequences of which can be measurable if the molecule involved is
critical.
When an atom is ionized, its chemical binding properties change. If
the atom is a constituent of a large molecule, ionization may result in
breakage of the molecule or relocation of the atom within the
molecule. The abnormal molecule may in time function improperly or
cease to function, which can result in serious impairment or death of
the cell.
This process is reversible. Ionized atoms can become neutral again
by attracting a free electron. Molecules can be mended by repair
enzymes. Cell and tissues can regenerate and recover from radiation
injury.
If the radiation response occurs within minutes or days after the
radiation exposure, it is classified as an early effect of radiation. On the
other hand, if the human injury is not observed for months or years, it
is called a late effect of radiation.
In addition, many other radiation responses have been experimentally
observed in animals. Most human responses have been observed to
occur after exposure to rather large radiation doses. However, we are
cautious and assume that even small doses are harmful.
The ultimate goal of radiobiologic research is to accurately
describe the effects of radiation on humans so that radiation
can be used more safely in diagnosis and more effectively in
therapy. Most radiobiologic research seeks to develop doseresponse relationships so the effects of planned doses can be
predicted and the response to accidental exposure managed
COMPOSITION OF THE BODY
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. More than 85% of the body consists of hydrogen and
oxygen.
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
Population
Effect
American radiologists
Atomic bomb survivors
Radiation accident victims
(e.g., Chernobyl)
Marshall Islanders
Uranium miners
Radium watch-dial painters
Patients treated with 131I
Children treated for enlarged
thymus
Children of Belarus (downwind
from Chernobyl)
Patients with ankylosing
spondylitis
Patients who underwent
Thorotrast studies
Irradiation in utero
Volunteer convicts
Cyclotron workers
Leukemia, reduced life span
Malignant disease
Acute lethality
Thyroid cancer
Lung cancer
Bone cancer
Thyroid cancer
Thyroid cancer
Thyroid cancer
Leukemia
Liver cancer
Childhood malignancy
Fertility impairment
Cataracts
Molecular Composition
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.
Water
The most abundant molecular constituent of the body is water. It
consists of two atoms of hydrogen and one atom of oxygen (H2O) and
constitutes approximately 80% of human substance. Humans are
basically made of structured water.
The water molecules exist both in the free state and in the bound
state, that is, bound to other molecules. They provide some form and
shape, assist in maintaining body temperature, and enter into some
biochemical reactions.
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.
Proteins have a variety of uses in the body. They provide structure and
support. Muscles are very high in protein content. Proteins also function as
enzymes, hormones, and antibodies.
Enzymes are molecules that are necessary in small quantities to allow a
biochemical reaction to continue, even though they do not directly enter
into the reaction.
Hormones are molecules that exercise regulatory control over some body
functions, such as growth and development. Hormones are produced and
secreted by the endocrine glands—the pituitary, adrenal, thyroid,
parathyroid, pancreas, and gonads.
Lipids
Lipids are organic macromolecules composed solely of carbon,
hydrogen, and oxygen.
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 .This structural difference
determines the contribution of the carbohydrate molecule to body
biochemistry. The ratio of the number of hydrogen atoms to oxygen atoms
in a carbohydrate molecule is 2:1 (as in water), and a large fraction of this
molecule consists of these atoms. Consequently, carbohydrates were first
considered to be watered, or hydrated, carbons, hence their name.
The chief function of carbohydrates in the body is to provide fuel for cell
metabolism.
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.
The nucleic acids are very large and extremely complex macromolecules.. DNA
consists of a backbone composed of alternating segments of deoxyribose (a
sugar) and phosphate. For each deoxyribose–phosphate conjugate formed, a
molecule of water is removed.
DNA is the radiation-sensitive target molecule
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
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
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.
The large bean-shaped structures are mitochondria. Macromolecules are
digested in the mitochondria to produce energy for the cell. The mitochondria
are therefore called the engine of the cell.
The small, dot-like structures are ribosomes. Ribosomes are the site of
protein synthesis and therefore are essential to normal cellular function.
Ribosomes are scattered throughout the cytoplasm or the endoplasmic
reticulum.
The small pea-like sacs are lysosomes. The lysosomes contain
enzymes capable of digesting cellular fragments and sometimes the
cell itself. Lysosomes help to control intracellular contaminants.
All these structures, including the cell itself, are surrounded by membranes.
These membranes consist principally of lipid-protein complexes that
selectively allow small molecules and water to diffuse from one side to the
other. These cellular membranes, of course, also provide structure and form
for the cell and its components.
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.
A number of experiments have shown that the nucleus is much
more sensitive than the cytoplasm to the effects of radiation. Such
experiments are conducted with the use of precise microbeams of
electrons that can be focused and directed to a particular cell part,
or through incorporation of the radioactive isotopes tritium (3H) and
carbon-14 (14C) into cellular molecules that localize exclusively to
the cytoplasm or the nucleus.