*** Week 5

Question 1

What is Radiobiology?

Answer 1

the study of radiation effects at the cellular and molecular level

Question 2

Describe the chain of events for how radiation affects cells.

Answer 2

• radiation results in random distributions of energy
• energy causes excitation and ionisation (chemical bond breakage)
• chemical bond breakage leads to molecular change and cell damage

Question 3

How long does it take for the biological effects, corresponding to the absorption of ionising energy?

Answer 3

10^-15 s to years

Question 4

For ionising radiation what are the physical, chemical and biological phases?

Answer 4

Physical: interaction of radiation with matter causing the formation of radicals
Chemical: when lesions in the DNA may accumulate
Biological: effects on organs and tissues

Question 5

What are the two factors that affect biological radio sensitivity?

Answer 5

physical factors, biologic factors

Question 6

Physical Factors: what is the Linear Energy Transfer (LET)?

Answer 6

measure of the rate at which energy is transferred from ionising radiation to soft tissue

Question 7

Physical Factors: what is the Relative Biologic Effectiveness?

Answer 7

expresses the relative effectiveness of different types of radiation in producing damage- (also termed as the tissue weighting factor)
RBE= dose of standard radiation (250keV x-rays) necessary to produce a given effect/ dose of another radiation source needed to produce the same biologic response

Question 8

Physical Factors: What is protraction and fractionation?

Answer 8

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

Question 9

What is Surviving Fraction (S)?

Answer 9

expresses the magnitude of the effect of a given dose of radiation on cells’ reproductive capacity
-S = number of cells serving a given dose/ number of cells in the original unexposed sample

Question 10

Biologic Factors: What is the oxygen effect?

Answer 10

tissues/cells are more sensitive in the presence of oxygen (aerobic state) than in “hypoxic” (low in oxygen)

• many tumours have areas of hypoxic cells
• hypoxic cells are therefore difficult to ‘kill’ with low LET radiation

Question 11

Biologic Factors: What is the oxygen enhancement radio (OER)?

Answer 11

ratio of doses which produce the same level of biological effect in hypoxic compared with oxygenated conditions:
OER = dose necessary in hypoxic conditions to produce a given effect/ dose necessary under aerobic conditions to produce the same effect

Question 12

Is the oxygen enhancement ratio dependent on LET?

Answer 12

yes

OER is highest for low LET radiation

Question 13

What are free radicals?

Answer 13

uncharged molecules containing a single unpaired electron, highly reactive

Question 14

Biological Factors:

what are the forms of radiation damage to cells?

Answer 14

• Damage to the nucleus and DNA
• Damage to the cell membrane
• Damage to the mitochondria in the cell’s cytoplasm
• Damage to lysosome (causes relate of enzymes which results in the cell self-digestion)

Question 15

What phase in the cell cycle is most radiosensitive?

Answer 15

tissues with high metabolic activity, long and dividing cells and tissues are more radiosensitive than mature cells
(e.g. fetes is considerable more sensitive to radiation exposure than the child or adult

Question 16

Do Fractionated doses or single doses of the same total level result in less cell killing?

Answer 16

cells exposed to fractionated dose experience less cell killing than for a single dose of the same total level

Question 17

Biologic Factors: What is the recovery effect?

Answer 17

time between the fractions where cells can recover

Question 18

What is the Elkind curve?

Answer 18

Describes the cell survival in terms of time between the fractions

Question 19

Biologic Factors: What is target theory?

Answer 19

for a cell to die after radiation exposure, its co-called target molecule must be inactivated
(DNA is the principal radiation-sensitive molecule/ target molecule)

Question 20

What are the types of DNA damage?

Answer 20

base damages
cross links between different strands of DAN
protein cross links
intercalation
point lesions
sing and double strand breaks

Question 21

What is the difference between a direct and indirect effect of I.R.?

Answer 21

Direct: if the initial ionising event occurs on the most radiosensitive molecule (which is DNA)
Indirect: if the initial ionising even occurs on any other molecule, usually water, which then transfers energy (damage) to the DNA

Question 22

What is radioanalysis?

Answer 22

The production and interactions of free radicals

Question 23

Which effect of IR causes more damage from low LET IR’s?

Answer 23

The indirect effect is the more important mechanism in causing damage from low LET IR’s (x-rays, electrons, gamma rays) (accounting for 2/3 of damage)

Question 24

Why is the indirect effect so damaging to DNA?

Answer 24

because a far-ranging/ long-lived radical can have many opportunities to interact and cause damage via the indirect effect

Question 25

What are two things that some areas of the tumour may suffer from?

Answer 25

• acute hypoxia (as a result of the temporary closing or blockage of blood vessels)
• chronic hypoxia (over long periods, as some cells are too far from the capillary for oxygen to diffuse to them)

Question 26

Describe the relation of the tumour cells to the capillary, and the effect that has on its oxygenation.

Answer 26

cells near a capillary are well oxygenated

cells more than 100micrometers from a capillary become hypoxic (some of these cells die)

Question 27

how do cell positions in relation to the capillaries, change after getting a diagnostic x-ray?

Answer 27

• the first fraction (dose) kills some of the hypoxic cells and a greater % of the oxygenated cells near the capillary
• the tumour therefore shrinks towards the capillary so that the hypoxic cells receive more oxygen
• therefore, these cells can be more easily killed

Question 28

What happens when high LET radiation is used to treat the hypoxic and aerated regions of a tumour?

Answer 28

the hypoxic regions and oxygenated regions receive the same damage when high LET radiation is used.
(therefore there is an interest in using neutrons and other high LET radiation for therapy)

Question 29

What are the three mathematical descriptions of the target theory?

Answer 29

single-target, single-hit model
multitarget, single-hit model
linear-quadratic model

Question 30

What is the single-target, single-hit model?

Answer 30

based on the single hit theory that within each cell there is a single target that must be ‘hit’ once by the IR to cause reproductive death
-random hit pattern is described by the Poisson distribution

Question 31

In the single-target, single-hit model, when the number of hits is equal to the number of cells, what percentage will be hit at least once and what will survive?

Answer 31

63% of the cells will be hit at least once (will be killed), and 37% will survive
-if there were no wasted hits, D37 (dose that results in 37% survival) is the dose that would be sufficient to kill 100% of the cells

Question 32

What does a low D37 represent?

Answer 32

high radiosensitivity 
(don't need much dose to kill 63% of cells)

Question 33

What does a high D37 represent?

Answer 33

radioresistance

need much more dose to kill 63% of cells

Question 34

What is the Multitarget, single-hit model?

Answer 34

assumes that within each cell there are multiple targets all of which must be hit once to cause reproductive death

• inactivation of a target is a sublethal (effect less than lethal) event
• therefore needs lots of hits to kill the cell (at low doses there is nearly 100% survival)

Question 35

What is the linear-quadratic model?

Answer 35

preferred model
assumes that there are two components to cell killing
-single event killing (e.g. double strand break caused by a single ionising particle)
-two event killing (e.g. double strand break caused by two separate ionising particles)
-the relationship has an initial non zero slope which agrees with the experiment but results in a bending curve (which may not be the case)