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Cellular Division
Cell Function
Every human cell has a specific function in supporting the total body. Some
differences are obvious, as in nerve cells, blood cells, and muscle cells.
Similarities are also somewhat obvious
In addition to its specialized function, each cell to some extent absorbs all
molecular nutrients through the cell membrane and uses these nutrients in
energy production and molecular synthesis. If this molecular synthesis is
damaged by radiation exposure, the cell may malfunction and die.
Protein synthesis is a good example of a critical cellular function necessary for
survival. DNA, located in the nucleus, contains a molecular code that identifies
which proteins the cell will make.
This code is determined by the sequence of base pairs (adenine–thymine and
cytosine–guanine). A series of three base pairs, called a codon, identifies one of
the 22 human amino acids available for protein synthesis.
This genetic message is transferred within the nucleus to a molecule of mRNA.
mRNA leaves the nucleus by way of the endoplasmic reticulum and makes its
way to a ribosome, where the genetic message is transferred to yet another RNA
molecule (tRNA).
tRNA searches the cytoplasm for the amino acids for which it is coded. It attaches
to the amino acid and carries it to the ribosome, where it is joined with other
amino acids in sequence by peptide bonds to form the required protein molecule.
Interference with any phase of this procedure for protein synthesis could result in
damage to the cell. Radiation interaction in which the molecule has primary
control over protein synthesis (DNA) is more effective in producing a response
than is radiation interaction with other molecules involved in protein synthesis
Cell division is the multiplication process whereby one cell divides to form two or
more cells. Mitosis (M) and meiosis are the two types of cell division that occur in
the body. When somatic cells (all cells in the human body except the germ cells)
divide, they undergo mitosis. Genetic cells (the oogonium, or female germ cell,
and the spermatogonium, or male germ cell) undergo meiosis.
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.
Through the process of mitosis (M), a parent cell divides to form two daughter
cells identical to the parent cell. This process results in an approximately equal
distribution of all cellular material between the two daughter cells. The cellular
life cycle may be pictured as in. Different phases of cell growth, maturation, and
division occur in each cell cycle. Four distinct phases of the cellular life cycle
are identifiable: M (mitosis phase), G1(pre-DNA synthesis phase), S (synthesis
phase), and G2 (post-DNA synthesis phase). Additionally, mitosis (M) can be
divided into four subphases: prophase, metaphase, anaphase, and telophase.
Mitosis is the division phase of the cellular life cycle. It is actually the last phase of
the cycle. After it has commenced, it takes only about 1 hour to complete in all
cells. Interphase, the period of cell growth that occurs before actual mitosis,
consists of three intervals: G1, S, and G2. G1, the earliest, is the phase between
reproductive events. It is the gap in the growth of the cell that occurs between
mitosis and DNA synthesis. Depending on the type of cells involved, this interval
may take just a few minutes or it may take several hours. G1 is designated as the
pre-DNA-synthesis phase. During G1 a form of RNA is synthesized in the cells that
are to reproduce. This RNA is needed before actual DNA synthesis can efficiently
The cell biologist usually identifies four phases of the cell cycle: M, G1, S, and
G2. These phases of the cell cycle are characterized by the structure of the
chromosomes, which contain the genetic material DNA. The gap in cell growth
between M and S is G1. G1 is the pre-DNA synthesis phase.
The DNA synthesis phase is S. During this period, each DNA molecule is
replicated into two identical daughter DNA molecules
During S phase, the chromosome is transformed from a structure with two
chromatids attached to a centromere to a structure with four chromatids attached
to a centromere.The result is two pairs of homologous chromatids, that is,
chromatids with precisely the same DNA content and structure.
The G2 phase is the post-DNA synthesis gap of cell growth
During interphase, the chromosomes are not visible; however, during mitosis, the
DNA slowly takes the form of the chromosomes as seen
microscopicallyschematically depicts the process of mitosis.
While the S phase is taking place, the chromosome changes in shape from a
figure with two chromatids connected to a centromere to a figure with four
chromatids connected to a centromere.
During prophase, the first phase of cell division, the nucleus enlarges, the
DNA complex (the chromatid network of threads) coils up more tightly, and
the chromatids become more visible on stained microscopic slides.
Chromosomes enlarge, and the DNA begins to take structural form. The
nuclear membrane disappears, and the centrioles (small hollow cylindrical
structures) migrate to opposite sides of the cell and begin to regulate the
formation of the mitotic spindle, the delicate fibers that are attached to the
centrioles and extend from one side of the cell to the other across the
equator of the cell.
As metaphase begins, the fibers collectively referred to as the mitotic spindle
form between the centrioles. Each chromosome (which now consists of two
chromatids) lines up in the center or equator of the cell attached by its
centromere to the mitotic spindle. This forms the equatorial plate. The
centromeres then duplicate, and each chromatid attaches itself individually to
the spindle. At the end of metaphase, the chromatids are strung out along the
mitotic spindle much like laundry hung on a clothesline. During metaphase, cell
division can be stopped and visible chromosomes can be examined under a
microscope. Chromosome damage caused by radiation can then be evaluated.
During anaphase, the duplicate centromeres migrate in opposite directions
along the mitotic spindle, carrying the chromatids to opposite sides of the cell.
The cell is now ready to begin the last phase of division.
During telophase, the chromatids undergo changes in appearance by uncoiling
and becoming long, loosely spiraled threads. Simultaneously the nuclear
membrane re-forms, and two nuclei (one for each new daughter cell) appear.
The cytoplasm also divides (cytokinesis) near the equator of the cell to surround
each new nucleus. After this cell division completes, each daughter cell has a
complete cell membrane and contains exactly the same amount of genetic
material (46 chromosomes) as the parent cell
Sensitivity – Cell Cycle Phase
Cells are most sensitive to radiation during mitosis (M phase) and RNA
synthesis (G2 phase)
Less sensitive during the preparatory period for DNA synthesis (G1
Least sensitive during DNA synthesis (S phase)
During mitosis (M), the metaphase is the most sensitive
Radiation-induced chromosome damage is analyzed during
Meiosis is a special type of cell division that reduces the number of
chromosomes in each daughter cell to half the number of chromosomes in the
parent cell. Male and female germ cells, or sperm and ova, of sexually mature
individuals each begin meiosis with 46 chromosomes. However, before the male
and female germ cells unite to produce a new organism, the number of
chromosomes in each must be reduced by one half to ensure that the daughter
cells (zygotes) formed when they unite will contain only the normal number of 46
chromosomes. Hence, meiosis is really a process of reduction division.
Paradoxically, meiosis begins with a doubling of the amount of genetic material; as
in mitosis, DNA replication occurs during interphase. As a result of DNA replication,
each one-chromatid chromosome duplicates, forming a two-chromatid
chromosome. This means that sperm and egg cells begin meiosis with twice the
amount of genetic material as the original parent cell. Thus, at the beginning of
meiosis, the number of chromosomes increases from 2n to 4n (n = 23).
The various phases of meiosis are similar to those occurring in mitosis. The major
difference between the two types of cell division begins at the end of telophase. In
meiosis, after the parent germ cell has formed two daughter cells, each of which (in
human beings) contains 46 chromosomes, the daughter cells divide without DNA
replication; chromosome duplication does not occur at this phase of division. These
two successive divisions result in the formation of four granddaughter cells, each of
which contains only 23 chromosomes. This means that the proper number of 46
chromosomes will be produced when a female ovum containing 23 chromosomes
is fertilized by a male sperm containing 23 chromosomes
During the development and maturation of a human from two united genetic
cells, a number of different types of cells evolve. Collections of cells of similar
structure and function form tissues.
These tissues in turn are precisely bound together to form organs. The tissues
and the organs of the body serve as discrete units with specific functional
responsibilities. Some tissues and organs combine into an overall integrated
organization known as an organ system.
The principal organ systems of the body are the nervous system, the digestive
system, the endocrine system, the respiratory system, and the reproductive
system. Effects of radiation that appear at the whole-body level result from
damage to these organ systems that occurs as the result of radiation injury to
the cells of that system.
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
Stem cells are more sensitive to radiation than mature cells
In 1906, two French scientists, Bergonie and Tribondeau, theorized and
observed that radiosensitivity was a function of the metabolic state of the tissue
being irradiated. This has come to be known as the Law of Bergonie and
Tribondeau and has been verified many times. Basically, the law states that:
the radiosensitivity of cell is directly proportional to their reproductive activity
and inversely proportional to their degree of differentiation.
Cells most active in reproducing themselves and cells not fully mature will be
most harmed by radiation.
The more mature and specialized in performing functions as cell is, the less
sensitive it is to radiation.
This law is principally interesting as a historical note in the development of
radiobiology. It has found some application in radiation oncology. In diagnostic
imaging, the law serves to remind us that the fetus is considerably more
sensitive to radiation exposure than the child or the mature adult
Radiosensitivity varies with age. Experiments with animals have shown that the
very young and the very old are more sensitive to radiation
The sensitivity of the cell to radiation is determined somewhat by its state of maturity
and its functional role. The tissues and organs of the body include both stem cells
and mature cells. Several types of tissue can be classified according to structural or
functional features. These features influence the degree of radiosensitivity of the
Cell Type
Intestinal crypt cells
Endothelial cells
Muscle cells
Nerve cells
Level of Radiosensitivity*
Tissue or Organ
High: 200 to 1000 rad (2 to 10 Gyt)
Lymphoid tissue
Bone marrow
Intermediate: 1000 to 5000 rad (10 to
50 Gyt)
Growing bone
Low: >5000 rad (>50 Gyt)
Growth arrest