Radiobiology

Question 1

Ionization

Answer 1

The process by which a neutral atom acquires a positive or negative charge.

Question 2

Excitation

Answer 2

Electrons raised to a higher energy level without actual ejection

Question 3

Directly ionizing radiation

Answer 3

Charged particle such as electrons, protons, heavy ions, alpha and beta particles. Interact directly with atoms through coulombic forces and transfer kinetic energy directly.

Question 4

Indirectly ionizing radiation

Answer 4

Photons (x-rays, gamma rays) and neutrons are charge less and therefore more penetrating. They have enough energy to fee an orbital electron which in turn is directly ionizing.

Question 5

LET

Answer 5

Linear energy transfer is the average energy deposited per unit length.
As LET goes up so does the number of specific ionizations.

Question 6

Specific ionizations

Answer 6

Number of ion pairs produced per unit length

Question 7

Direct action

Answer 7

DNA damage caused directly by radiation

Question 8

Indirect action

Answer 8

DNA damage due to chemical reactions caused by radiation. Radiation interacts with other atoms or molecules. Is the dominant process for low LET.

Question 9

Stages of the cell cycle

Answer 9

Interphase: part of the cell cycle when cells are not actively dividing.

• G1: gap between telophase and DNA synthesis
• S phase: DNA synthesis
• G2: the gap between DNA synthesis and the first phase of mitosis

Mitosis

• prophase: centrioles move to opposite poles and start to form spindles. Chromosomes start to be seen as threads and be visible as they move to the equator.
• metaphase: centromere of a chromosome attached to spindle fibre at equator.
• anaphase: Centromeres have divided and single chromosomes are moving to opposite end of the cell.
• telophase: cell is divided.

Question 10

Synchronous cell growth

Answer 10

All cells are at the same point of the cell cycle. Used for research purposes.

Question 11

A synchronous cell growth

Answer 11

Cell are all in different stages of the cell cycle. Represents real life situations. Where the cells are in the cell cycle will impact how they respond to radiation.

Question 12

3 fates of irradiated cells

Answer 12

Division delay: cells are prevented from entering mitosis. Can happen in both lethally and non-lethally damaged cells. Cells not in mitosis are delayed in G2.

• mitotic index: the ratio in cells in mitosis at any one time usually constant but radiation can impact the index.
• mitotic delay: due to radiation there is a reduced amount of cells in mitosis.
• mitotic overshoot: at lower doses cells recover from mitotic delay and add to the normal amount of cells in mitosis. Results in an increase in the mitotic index. Will return to normal after radiation.

Interphase death: occurs in cells that do not divide. The radiation breaks the DNA into pieces which causes apoptosis. Occurs at high doses and no mitotic overshoot occurs.

Reproductive failure: when cells are unable to divide due to break in chromosome.

Question 13

Sub lethal damage

Answer 13

Smaller dose given over time allows healthy tissue time to repair themselves

Question 14

Most sensitive phase of the cell cycle

Answer 14

G2 and M phases
Less sensitive in G1
At low doses progression into mitosis is delayed.

Question 15

Least sensitive phase of the cell cycle

Answer 15

Late S
Early S is more sensitive
G1 is more sensitive
At higher doses all phases of the cell cycle can be effected (radiosenstive and radioresistent)

Question 16

Intracellular repair

Answer 16

Cells ability to repair sub-lethal damage. Occurs when radiation is delivered in fractions. Each time the survival curve has the same D0, n and Dq therefore a higher total dose is needed for the same biological effect.

Question 17

Factors that effect the response of cells and tissues to radiation

Answer 17

Biological factors: phase of cell cycle, intracellular repair
Physical factors: LET, RBE and dose rate
Chemical factors: sensitizers and protectors

Question 18

High LET

Answer 18

Particles:
- neutrons
- alpha particles
- electrons
Characteristics
- superficial
- direct damage
- Densely ionizing

Question 19

Low LET

Answer 19

Particles:
- x-rays
- Gamma rays
characteristics
- Penetrating
- Indirect damage
- sparsely ionizing

Question 20

RBE

Answer 20

Relative biological effectiveness. Equal doses of two different types of radiation do not produce the same biological effect. RBE relates radiation quality to biological response.

Question 21

3 factors that contribute to the dose rate effect

Answer 21

Repair: reducing the dose rate makes the survival curve more shallow can causes the shoulder to disappear. At low dose rates the damage may be sublethal. The dose is not enough to kill the cell and the cell has a chance to recover.
Redistribution: with some cell line a reduction in dose rate results in a steeper cell curve. This is because lowering the dose of allows all cells to progress through the cell cycle and accumulate in G2 a radio sensitive phase.
Proliferation: further reduction in dose rate allows cells to pass through the G2 block and divide. Proliferation occurs during an exposure if the dose rate is low enough and time is long compared to the mitotic rate.

Question 22

Two chemical factors that impact of the response of the cell to radiation

Answer 22

Sensitizers

Protectors

Question 23

Chemical senstizers

Answer 23

Increase the killing effect of the given dose of radiation. Goal is to find an agent that shows a differential effect between tumor and normal tissue.

Oxygen is the universal enhance of radiation effects.

Question 24

Oxygen enhancement ratio

Answer 24

OER, the ratio of hypoxic cells to aerobic doses needed to achieve the same result.

Not constant for the whole dose range. OER is lower for lower doses, due to cells in the cell cycle. Cells in G1 have lower OER and are more radio sensitive so they dominant at lower dose region of the survival curve.

With high LET radiation the amount of damage would not be repairable therefore the presence of oxygen would not further enhance response.

Question 25

Why is there an oxygen effect?

Answer 25

Free radicals break chemical bonds which produce chemical changes initiating a chain of events resulting in biological damage.

Question 26

Hypoxic cell sensitizers

Answer 26

mimic oxygen, making hypoxic cells more sensitive. Increases the radio sensitivity of cells that are deficient of oxygen.

Question 27

Chemical protectors

Answer 27

Agents that reduce the effect of radiation on the cells. It must be present at the time of radiation to have an effect. Work as free radical scavengers. Most efficient at low LET.

Question 28

Response of tissue or organs depends on:

Answer 28

- inherent senstivity of cells in that organ or tissue | - turnover kinetics of different cells (whether dividing or not and if so what is the rate of division)

Question 29

Parenchymal tissue

Answer 29

Tissues if made of cells characteristics of that tissue or organ and its functional cells.

Question 30

Stromal tissue

Answer 30

Composed of connective tissue and vasculature that supports the organs parenchyma for its structure and function.

Question 31

Acute responding tissue

Answer 31

``` Typically seen within 10 days of starting treatments. Typically happen in tissues with high rapid turnover rate. High alpha/beta ratio Examples: Skin Jejunum Colon Testis ```

Question 32

Late responding tissue

Answer 32

``` Damage not evident until cells begin to divide. Occur in predominantly in slow proliferating tissues and appear after a delay of several months or years after radiation. Low alpha/beta ratio Examples: Spinal cord Kidney Lung Bladder ```

Question 33

Functional subunits (FSU's)

Answer 33

Concept used to model the radiation response of normal tissues. It is a compartment of an organ that performs part of the organ function. Can be arranged in serial, parallel or both.

Question 34

Structurally defined FSU's

Answer 34

Each FSU is independent of its neighbor. The survival of FSU is depending on one or more clonogenic cells surviving within it. If all FSU's are irradiated and all clonogenic cells are killed the organ will no longer function. If only a small portion of the organ is irradiated to a high dose it will continue to function. Ex. Kidneys

Question 35

Structurally undefined FSU's

Answer 35

Not independent of neighbor. Cologenic cells can migrate from one FSU to another if one is depleted another can migrate and repopulate a depleted FSU. Ex. Skin

Question 36

Serial organs

Answer 36

When FSU's are arranged in a series, like links in the chain. If one link is broken the chain can no longer function. If a single FSU fails than the organ experiences detrimental effects. Examples: - spinal cord - GI tract These organs are susceptible to high point doses. Death in any segment along the organ will result in failure of the organ. Have a threshold dose any dose below normal function is maintained. In the spinal cord myelopathy can increase with increased volume at lower doses most likely due to damage of the vasculature rather than damage to the nerve cells.

Question 37

Parallel organs

Answer 37

The organ is not dependent on all FSU's functioning. Only about 30% of FSU's are required to maintain function. Each FSU is able to function independently of each other. Loss of a single FSU leads to a slight decrease in function of the organ. Are more sensitve to volume effects. Sensitive to the irradiation of the whole volume but small volumes can be treated with much higher doses. Functional damage will not occur until a critical number of FSU's are deactivated. Ex. liver and kidneys

Question 38

Example of organs that are a combination of serial and parallel

Answer 38

Lungs | Brain

Question 39

General organ changes

Answer 39

Acute: inflammation, edema, loss of mucosal surfaces Late: fibrosis, atrophy, ulceration, stricture, stenosis, obstruction Necrosis is the ultimate result of failure to repair

Question 40

Healing occurs by

Answer 40

Regeneration | Repair

Question 41

Regeneration

Answer 41

Replacement of damaged cells by the same type of cell. Results in total or partial reversal of early radiation damage. Acutely responding tissue will undergo regeneration at all dose levels unless target cells are destroyed than repair would take place. Late responding tissues have minimal regeneration capabilities. therefore moderate to high doses will result in repair.

Question 42

Repair

Answer 42

Replacement of the depleted original cell by a different type of cell. It does not restore the organ to the pre-radiation conditions. It can produce secondary chronic effects.

Question 43

TD5/5

Answer 43

Minimum tolerance dose. The dose to which a given population of patients is exposed under standard treatment conditions resulting in no more than 5% severe complications within 5 years after treatment.

Question 44

TD50/5

Answer 44

Maximum tolerance dose. The dose at which a given population of patients exposed under standard set of treatment conditions resulting in no more than 50% severe complications within 5 years of treatment.

Question 45

5 R's of radiobiology

Answer 45

``` Repair Regeneration/re population Re oxygenation Redistribution Radio sensitivity ```

Question 46

Pros and cons of fractionation on normal tissues

Answer 46

Advantages: - spares tissue by repair of sublethal damage - reducing fraction size greatly reduces reactions in late responding tissues - repopulation/regeneration if overall time is sufficiently long (acute responding tissue only) Disadvantage: - reassortment increases damage to cells by moving them into sensitive phases of the cell cycle

Question 47

Pros and cons of fractionation on tumors

Answer 47

Advantages: - reassortment increases damage to cells by moving cells into sensetive phases of the cell cycle - reoxygenation increases damage Disadvantages: - of overall time is too long, tumour cells repopulate during treatment

Question 48

Hyperfractionated

Answer 48

Delivering the dose in twice as many fractions in about the same overall time by giving two treatments per day. The overall dose is increased as each fraction is smaller.

Question 49

Accelerated treatment

Answer 49

Delivering dose to the same total dose in a much shorter time by delivering more than one fraction per day. Acute effects are the dose-limiting factor required reducing fraction size or to have a break during treatment. Purpose is the reduce repopulation in rapidly proliferating tumors with little or no chance in late effects.

Question 50

Hypofractionation

Answer 50

Smaller number of larger sized fractions. IMRT has improved dose distributions lowering dose to normal tissues the possibility of fraction size could be increased without increasing late effects.