L 3: Cell survival curves

Question 1

Cell Survival curve

Answer 1

• It is the relationship between radiation dose and the proportion of cells that survive.
• Basically the loss of reproduction capacity.

Question 2

Types of cell death that can occur

Answer 2

• Mitotic death
• Apoptosis

Question 3

Mean lethal dose

Answer 3

Usually less than 2Gy

Question 4

Dose required to destroy cell function

Answer 4

100 Gy

Question 5

Plating efficiency

Answer 5

• It is the % of cells seeded which grow into colonies
• PE= No of colonies counted / No of colonies seeded x 100

Question 6

Surviving fraction

Answer 6

• It is the ratio of colonies produced to cells plated, with a correction necessary for plating efficiency.
• SF = Colonies counted/cells seeded x (PE/100)

Question 7

Survival curves

Answer 7

Linear Scale: Dose
Log scale: Surviving fraction
* Two models to describe the curve: Multitarget model and linear quadratic model

Question 8

Low LET

Answer 8

Eg: X-rays
* straight and then slope
* Suvriving fraction is the exponential of dose
* High dose = curvier slope

Question 9

High LET

Answer 9

Eg: alpha particles
* Curve is a straight line

Question 10

Multitarget model

Answer 10

• Ancient model not currently used
• Initial Slope = D1
• Final slope = Do
• Width of the shoulder = n or Dq
• Final slope results from multiple event killing.

Log e n=Dq/D0
S=0.37

Question 11

Linear Quadratic Model

Answer 11

Most accurate
* A/B ratio, has these 2 parameters in the formula
* Linear part: Shoulder, double hit, alpha
* Quadratic part: straight line, single hit, beta
* High LET: double hit, alpha component
* Low LET: Single hit, beta component
* The curve continues to bend downwards indefinitely with increasing dose.
* advantage : It accurately represents the initial dose response shoulder

Question 12

Bystander effect

Answer 12

Induction of biological effects in cells that are not directly traversered with charged particles but are in proximity to the cells that are get irradiated.

Question 13

Common form of cell death post radiation

Answer 13

Mitotic cell death
* Cells die due to damaged chromosomes.

Question 14

Proto-oncogenes

Answer 14

N-ras
raf
ras
myc

Question 15

Increases radio-sensitivity by reducing the ability to repair the DS DNA breaks

Answer 15

Ku-80
Ku-70
XRCC-7

Question 16

A/B

Answer 16

• A/B ratio at which the linear and quadratic contributions to cell killing are equal.
• a/b=dose in Gy at which contribution to killing from a (non-repairable damage) is equal to b (repairable damage)
  a =Non repairable damage: single track component, cell is inactivated after 1e- track causes 2 chromosomal breaks in a critical target
  b =Repairable damage: portion of survival subject to multiple e- tracks; if hits do not accumulate rapidly, repair intervenes

Question 17

Alpha

Answer 17

Every extra Gy of radiation you give in a single dose you get fairly linear increase in killing

Question 18

Beta

Answer 18

does increasing the dose lead to increase in cell killing

Question 19

High LET

Answer 19

No A/B ratio as all the killing is by alpha alone.
alpha is very very high
straight line on the curve

Question 20

D0 and n

Board question

Question 21

• Straight line on the curve is seen when
• Single hit single target

Answer 21

• Defects in DNA repair mechanism
• High LET
• M Phase
  S=N/N0 =e-D/D0 where N=number of cells surviving dose D, N0= initial number of cells, D0=constant dose related to sensitivity

Question 22

D1
D0
n
Dq

Board question

Answer 22

D0= Must be on the quadratic part, reduction of cells by 37%

Question 23

Types of cell death

Board Question

Answer 23

Question 24

Necroptosis

Answer 24

• Programmed cell death in the form of necrosis
• Caspase independent
• found in RT exposure as well
• RIP kinase

Question 25

Pyroptosis

Answer 25

* Fever response ~ microbial infection * Inflammatory form of apoptosis. * Flagellin: induces pyroptosis * DAMP protein

Question 26

Ferroptosis

Answer 26

* Programmed cell death dependent on Fe. * PUMA protein

Question 27

Comparing all three

Answer 27

Question 28

Autophagy

Answer 28

* Cell suicide

Question 29

Apoptosis | Board question

Answer 29

* p-53 dependent * BCL 2 is a supressor of apoptosis * Lack of BH4, which is usually present in pro survival cells * Programmed cell death * Part of usual embryonic development T-cell differentiation * Affects scattered cells * Uses energy * “suicide” * no tissue disorganization – dead cells are “squeezed out” * **Lymphoma ** > Carcinoma > Sarcoma (absent) * Cytochrome "c" - indicator of apoptosis

Question 30

Mitotic Cell death | Board question

Answer 30

* Cells die while attempting to divide * May make 1 or few mistakes * Dominant cause of cell death when reproductive integrity is assumed *

Question 31

Must learn, Board question | BOard question

Answer 31

Oncogenes: Radioresistance * Raf overexpression * N-, H- and K-ras point mutations Did not affect cell cycle --> only G2 delay * Bcl2 overexpression * Her2/neu overexpression

Question 32

Least stable compound related to ionizing radiation

Answer 32

Water ion radical (H2O+) It has an unpaired electron

Question 33

Radioprotective agents are useful for

Answer 33

x-rays as they cause indirect damage.

Question 34

Sublethal damage

Answer 34

The effect of dose rate on sublethal damage repair is the greatest between 0.01-1Gy/Min. It causes greatest change in the slope of the cell survival curve

Question 35

which tumor has highest a/b ratio

Answer 35

SCCa of H & N

Question 36

Which tumor has lowest a/b ratio

Answer 36

Adenocarcinoma of the prostate