Cellular Effects of Ionising Radiation Flashcards
Radibiology effect levels
Cellular level: cells are as the basic functional unit of all
plants and animals.
Molecular level: the human body is composed of mostly
water, protein, lipid, carbohydrates, and nucleic acids such as
DNA.
The chain events of ionising radiation
Physical, chemical and biological
Physical phase
interaction of radiation with matter & formation of radicals which can cause indirect radiation damage to the cell.
Chemical Phase
when
lesions in the DNA may
accumulate.
Biological Phase
the final effect on organs and tissues - remainder of the repair processes, further cell divisions, mitotic death, etc.
Factors affecting biological radio sensitivity
Physical and biologic factors
Physical factors
dose: the quantity of the radiation absorbed by the cell or tissue
Type of radiation: LET and RBE
Biologic factors
Cell type
Phase of the cell cycle, age
Time between fractions/recovery effect
LET
measure of the rate at which energy is transferred
from ionising radiation to soft tissue
Unit: keV/µm
RBE
Equal doses of different types of radiation do not produce equal
biologic effects. Ratio comparing two types of radiation
Protraction
the dose is delivered continuously but at a lower
dose rate, allowing time for cell repair and tissue recovery.
Fractionation
the dose is delivered in a number of separate
fractions over a long time. Cell repair and recovery occur
between doses. This is used routinely in radiation oncology.
Surviving Fraction
expresses the magnitude of the effect
of a given dose of radiation on cells reproductive capacity
The lethal effects of radiation are determined by observing cell
survival, not cell death.
Difference in curves of single and fractionated dose
Single dose: initial “shoulder” on the curve indicating “accumulation of sublethal damage, followed by almost exponential decrease in surviving fraction.
Fractionated dose: repopulation and
recovery occur between multiple doses
– not necessarily at a constant rat
What type of radiation is better at cell killing
High LET Radiations such as
neutrons and protons etc are
more effective at cell killing than
low LET radiations.
Explain the oxygen effect
Tissues/cells are more sensitive in the presence of oxygen (aerobic
state) than in “hypoxic” (low in oxygen).
The oxygen effect is particularly important in radiotherapy since
many tumours have areas of hypoxic cells (abnormally low levels of
oxygen).
Hypoxic cells are therefore difficult to ‘kill’ with low LET radiation
(radioresistant).
OER
is the ratio of doses which produce the same level of biological
effect (e.g. level of survival) in hypoxic compared with oxygenated
conditions
Free radicals
uncharged molecules containing a single unpaired electron.
highly reactive.
Forms of radiation damage to the cell
- Damage to the nucleus and DNA
- Damage to the cell membrane
o May be ruptured allowing extracellular fluids to enter the cell and
it ‘drowns’,
o Rupturing also allows leakage of cell ions and nutrients. - Damage to the mitochondria in the cell’s cytoplasm
o Interrupts the cell’s food supply - Damage to lysosomes
o Causes release of enzymes which results in the cell digesting it’s
own internal structures (i.e. it eats itself)
Cell damage can result from which possible outcomes
- Injured or damaged cells may repair themselves
through the body’s defence mechanisms, resulting in
no residual damage - The cell might die and be replaced through normal
biological processes - The cell might incorrectly repair itself, resulting in a
viable but modified cell.
What is the target molecule
DNA
DNA damage
base damages (over 100 different types)
cross links between different strands of DNA,
protein cross links,
Intercalation (the reversible inclusion or insertion of a molecule or ion into
compounds with layered structures),
- Point Lesions
- Single and double strand break
These are potentially reversible (can be repaired) although the greater
the damage the less likely that the repair will be error free.
The outcome may be cell death, malignant disease or genetic damage.
Direct and indirect effects of IR
Direct Effect: if the initial ionising event occurs on the most
radiosensitive molecule which is DNA.
Indirect Effect: if the initial ionising event occurs on any other
molecule, usually water, which then transfers energy (damage)
to the DNA
Why is indirect effect damaging
a long-lived or far-ranging radical
can have many opportunities to interact and
cause damage via the indirect effect due to the large structure of DNA
Indirect effect of IR in a tumour
acute hypoxia as a result of the temporary closing or
blockage of blood vessels, or from
o chronic hypoxia
over long periods, as some cells are too
far from the capillary for oxygen to diffuse to them
Oxygen Effect and type of radiation
When high LET radiation is used, the hypoxic regions of a tumour are equally (or nearly equally) damaged to the aerated regions. There is interest in using neutrons and other high LET radiations for therapy.
Mathematical description of target theory
Single-Target, Single-Hit Model
Multitarget, Single-Hit Model
Linear-Quadratic Mode
Single target model theory
Start with 100 cells and ascribe a random hit pattern:
o After one hit, one of the 100 cells has been hit and killed.
o At the second hit, there’s a 99% chance that it will hit a different cell to the
first hit and a 1% chance that it will re-hit the first cell.
When the number of hits is equal to the number of cells, 63% of the
cells will be hit at least once (will be killed), and 37% will survive
Multitarget single hit model
The model assumes that within each cell there are multiple targets all of
which must be hit once to cause reproductive death (i.e. like the single hit
model but all targets must be inactivated to kill the cell).
Inactivation of a target is a sublethal event.
So in the first few hits, it’s really unlikely that there is damage done to the
cells, and normally it takes quite a few hits before damage is being done.
After many hits it’s highly likely that most cells have been hit at least once.
Linear Quadratic Model
This is currently the preferred model and assumes that there are two
components to cell killing:
One due to single event killing (e.g. double strand break caused by a
single ionising particle). The probability of NO damage is e
-αD
The other one due to two event killing (e.g. double strand break caused
by two separate ionising particles). The probability of NO damage is e
-βD
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