Rad Bio
Chapter 3 Lecture Notes
Law of Bergonie and Tribondeau? Immature cells will be most sensitive, i.e.
undifferentiated, precursor, or stem cells.
Some of most sensitive include lymphocytes, spermatogonia, erythroblasts, and intestinal
crypt cells.
Intermediate sensitivity – endothelial cells, osteoblasts, spermatids, and fibroblasts
Low radiosensitivity – muscle and nerve cells, and chondrocytes
General theory is that cells undergoing mitosis are most radiosensitive, from the mid to
late S-phase (synthesis phase – metaphase thru telophase). The nucleus is more
radiosensitive than cytoplasm, with DNA being the most radiosensitive.
3 possible outcomes of irradiation of cells (p.28): slowing down of mitosis, interphase
death, and cell death.
Slowing of mitosis – or division delay, occurs when low doses of radiation are
administered. The cause is unknown.
Interphase death – cell death before entering mitosis, occurs more frequently in cells with
high mitotic rates. This prevents cells from reproducing.
Factors for observing effects of cell irradiation:
1. matter of chance and probability that radiation will interact. Could or couldn’t be
cell damage
2. first deposit of radiation is given rapidly
3. interaction with cells is random
4. it’s impossible to tell if visible changes are the result of x-ray interaction or other
sources
5. biologic changes occur over a period of time, which is dose-dependent
Cell response factors include LET (linear energy transfer), RBE (relative biological
effectiveness, and OER (oxygen enhancement ratio).
LET (kilo-electron volts per micrometer) – measures rate at which energy is deposited as
a charged particle travels through matter. Think of LET as ability to ionize. X-rays and
gamma rays have low LET, meaning they lose or deposit their energy when passing
through tissue. Alpha and neutron radiation have high LET. An increase in LET means
and increase in chance for biologic interaction. Diagnostic x-rays have LET of
3keV/micrometer. See table 3-1 (p.29).
RBE – describes the effect of radiation with different LET’s
RBE = dose in rads from 250keV x-ray necessary to produce a given effect
dose in rads of test radiation necessary to produce the same effect
Example, p.30
RBE = 300rad = 3
100rad
Factors that influence RBE are radiation type, cell or tissue type, physiologic condition,
results being examined, and radiation dose rate.
As RBE increases, LET increases; diagnostic x-rays have an RBE of 1
Review chart on p.30
Oxygen Enhancement Ratio
Oxygen effect – response of tissue to radiation in an oxygenated environment greater
than in without oxygen.
OER = dose that produces a given biologic response under anoxic conditions
dose that produces the same biologic response under aerobic conditions
OER is dependent on LET. It is more pronounced with low LET radiation, because it is a
much smaller noticeable difference. Compare number of pebbles shattered from a
firecracker to number of pebbles shattered from an atomic bomb. High LET is too
destructive to notice such a minute change.
Example, p.32
OER = 5,000 = 5
1,000
Age influences radiosensitivity – the older we get, the more resistant to radiation we are.
Gender also influences radiosensitivity – women are 5-10% less radiosensitive than men.
Direct vs. indirect effects
Direct effect – when ionization takes place on a molecule, damaging that molecule or its
genetic structure.
Indirect effect – ionization occurs on a distant noncritical molecule, but ionization energy
transfers to another molecule, causing damage.
It is theorized that the majority of radiation effects in the body are a result of indirect
effects, with ionization happening initially with water in our body.
Radiolysis of water – irradiation of water which produces free radicals (uncharged
molecules containing a single unpaired electron in the valence shell). The ion pair (H+
and OH-) can combine with other molecules or react chemically and damage cells. The
free radicals become chemically unstable and highly reactive.
Three primary effects of irradiating macromolecules:
1. main-chain scission – link is cut or broken in long-chain molecules
2. cross-linking – spur-like extensions of the main chain link with other molecules,
or other parts of different molecules.
3. point lesions – affects individual bonds (hydrogen bonds of DNA), causing
molecular changes leading to abnormal cell function.
Order of chain molecule sensitivity:
1. DNA
2. RNA
3. protein molecules
Changes that can occur:
1. DNA damage resulting in cell death or metabolic changes (either stop
proliferation or have uncontrolled proliferation – Ca).
2. base sequences change, altering genetic blueprints for future generations
(mutation)
3. change or loss of a base, also a genetic mutation
All of these are termed point mutations, occur at low LET, and can sometimes be
repairable.
Radiation interaction may result in many variances of splitting chromosomes as well.
See chart on p. 37 for possible aberrations. It can result in single chromosome hits or
multiple with many defects or rearrangements of genetic material (called translocations).
Dose Response – graphic relationships between observed effects and radiation doses that
differ in 2 ways:
1. they are either linear or nonlinear
2. they are either threshold or nonthreshold
Linear – response is directly proportional to dose
Nonlinear – not directly proportional (double dose does not equal double response)
Threshold – radiation level below observable effects
Nonthreshold – assumes any radiation dose produces an effect
Diagnostic x-rays use a linear, nonthreshold dose response curve
Target theory – idea that molecules within cells that are abundant and are irradiated may
not cause permanent damage to the cell, but cell death will occur if the target molecule is
irradiated (DNA). This can be caused by direct or indirect irradiation.
