Cellular Effects of Ionising Radiation

Question 1

Radibiology effect levels

Answer 1

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.

Question 2

The chain events of ionising radiation

Answer 2

Physical, chemical and biological

Question 3

Physical phase

Answer 3

interaction of radiation with matter & formation of radicals which can cause indirect radiation damage to the cell.

Question 4

Chemical Phase

Answer 4

when
lesions in the DNA may
accumulate.

Question 5

Biological Phase

Answer 5

the final 
effect on organs and tissues -
remainder of the repair 
processes, further cell 
divisions, mitotic death, etc.

Question 6

Factors affecting biological radio sensitivity

Answer 6

Physical and biologic factors

Question 7

Physical factors

Answer 7

dose: the quantity of the radiation absorbed by the cell or tissue
Type of radiation: LET and RBE

Question 8

Biologic factors

Answer 8

Cell type
Phase of the cell cycle, age
Time between fractions/recovery effect

Question 9

LET

Answer 9

measure of the rate at which energy is transferred
from ionising radiation to soft tissue
Unit: keV/µm

Question 10

RBE

Answer 10

Equal doses of different types of radiation do not produce equal
biologic effects. Ratio comparing two types of radiation

Question 11

Protraction

Answer 11

the dose is delivered continuously but at a lower

dose rate, allowing time for cell repair and tissue recovery.

Question 12

Fractionation

Answer 12

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.

Question 13

Surviving Fraction

Answer 13

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.

Question 14

Difference in curves of single and fractionated dose

Answer 14

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

Question 15

What type of radiation is better at cell killing

Answer 15

High LET Radiations such as
neutrons and protons etc are
more effective at cell killing than
low LET radiations.

Question 16

Explain the oxygen effect

Answer 16

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).

Question 17

OER

Answer 17

is the ratio of doses which produce the same level of biological
effect (e.g. level of survival) in hypoxic compared with oxygenated
conditions

Question 18

Free radicals

Answer 18

uncharged molecules containing a single unpaired electron.

highly reactive.

Question 19

Forms of radiation damage to the cell

Answer 19

• 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)

Question 20

Cell damage can result from which possible outcomes

Answer 20

1. Injured or damaged cells may repair themselves
   through the body’s defence mechanisms, resulting in
   no residual damage
2. The cell might die and be replaced through normal
   biological processes
3. The cell might incorrectly repair itself, resulting in a
   viable but modified cell.

Question 21

What is the target molecule

Answer 21

DNA

Question 22

DNA damage

Answer 22

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.

Question 23

Direct and indirect effects of IR

Answer 23

 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

Question 24

Why is indirect effect damaging

Answer 24

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

Question 25

Indirect effect of IR in a tumour

Answer 25

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

Question 26

Oxygen Effect and type of radiation

Answer 26

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.

Question 27

Mathematical description of target theory

Answer 27

 Single-Target, Single-Hit Model
 Multitarget, Single-Hit Model
 Linear-Quadratic Mode

Question 28

Single target model theory

Answer 28

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

Question 29

Multitarget single hit model

Answer 29

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.

Question 30

Linear Quadratic Model

Answer 30

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
2