Biological Effects of Ionising Radiation Flashcards
What is radiobiology?
Radiobiology is a field of clinical medical sciences that
involves the study of the action of ionising radiation on living
things, especially health effects of radiation.
Units of radiation
Becquerel (Bq) is a
measure of radioactivity
(atom decays over time) –
so how many apples are
falling out of the tree
Bq=disintegrations/second
Gray (Gy) is a measure of
absorbed dose – how many
apples are hitting the
person
Gy=1 joule of radiation per
kg of matter
Sievert (Sv) is a measure
of effect on the body based
on the size and shape of
the apples, where the body
was hit
Sv=equivalent biological
effect of 1 joule/kg
How do we quantify radiation
‘dangerous-ness’
Linear Energy Transfer (LET)
How do we quantify radiation
‘dangerous-ness’
Linear Energy Transfer (LET)
Linear Energy Transfer (LET)
Linear Energy Transfer (LET)
+ LET is the rate at which energy is deposited as a charged
particle or photon travels through matter
+ Heavier particles with a larger charge produce higher
ionisation density
+ For a given particle type, as the velocity and energy goes
up, the density of ionisation (and therefore LET) reduces
Typical LET values
Alpha particles LET=100-200keV/ μm
14MeV neutrons LET=12keV/ μm
250kVp xrays LET=2keV/ μm
4MeV xrays LET=0.3keV/ μm
Relative Biological Effectiveness
(RBE)
+ Absorbed dose can be a poor indicator of the biological effect
of radiation
+ Biological effect can depend on many factors:
type of radiation, initial energy and type of tissue
1Gy of neutrons produce a greater biologic effect than 1Gy of xrays due to the
difference in the pattern of energy deposition
+ RBE is the ratio of biological effectiveness of one type of
ionising radiation compared to another
How does radiation damage tissue?
+ Direct damage of radiation causes a disruption in the
atomic structure which produces chemical and biological
changes to the DNA
+ Indirect damage of radiation is caused by the free radicals, which come from the ionisation or excitation of
the water component in the cells by producing a hydroxyl
radical (this accounts for 2/3rds of radiation damage)
ionizing radiation
direct damage
- double strand break/ single strand break
cell death - apoptosis
indirect damage
free radicals and reactive oxygen species
o2 - OH, h2O2 etc
double strand break/ single strand break
cell death
The cell cycle
The cell cycle
+ G1 phase= Metabolic changes prepare the cell for division –
signal is given to divide
+ S phase= DNA synthesis and replicates the genetic material each 46 cell is duplicated
+ G2 phase= Metabolic changes necessary for mitosis and
cytokinesis
cell checks the duplicated chromosomes for errors checks any errors. - check point gene - cell divides mitosis
+ M phase= A nuclear division (mitosis) followed by a cell
division (cytokinesis).
if you don’t have good checkpoint genes your cells will be sensitive to radiation - cells are killed easier - could be become cancerous
Cell check point genes
Cell check point genes
+ Cell cycle progression is monitored by molecular check
point genes
+ Genes involved in radiation effects halts in G2 so that
damage can be checked, and reparation started before
mitosis is started
+ Cells which lack check point genes are sensitive to
radiation-induced cell kill and carcinogenesis
genomicnic instablity - cells find it hard to repair
Mechanism of cell death
Mechanism of cell death
+ Mitotic death: when cells die attempting to divide (most
common)
+ Apoptosis: naturally programmed cell death
+ Bystander effect: cells directly affected by radiation
release cytotoxic molecules prompting death in
neighbouring cells
Types of cell death
Types of cell death
The definition of cell kill varies depending on the type of tissue:
+ Differentiated cells which do not proliferate (nerves, muscles,
secretory) are defined as loss of a specific function.
+ Proliferating cells (stem cells in bowel) are defined as a loss
of reproductive capacity.
Early and late responding tissues
Early and late responding tissues
+ Rapidly dividing cells respond early to radiation damage
(skin, intestinal epithelium, bone marrow)
+ Late responding tissues (spinal cord, lung, kidney)
+ All tissues have a natural tolerance for radiation damage
Cancer
Cancer
Cancer occurs when a normal cell:
+ has a mutation/loss of cell check point genes
+ loses the ability to stop reproducing
+ loses the ability to undergo apoptosis
