Cell death, Cell tissue/survival assays, models of cell survival

Question 1

executioner caspases

Answer 1

Caspase-3, -6, -7

Question 2

Senescence

Answer 2

Permanent arrest in G1

Cell aging, they lose the ability to divide. Can also be induced by radiation.

Question 3

Extrinsic apoptotsis pathway Initiator

Answer 3

Caspase 8

Question 4

Hallmark of apoptosis

Answer 4

Chromatin condensation, large nucleus, membrane blebbling

Question 5

4 R’s

Answer 5

Repair
Redistribution
Repopulation
Reoxygenation (last step)

Question 6

Quiescence

Answer 6

reversible, physiological, G0.

Question 7

Terminal differentiation

Answer 7

Irreversible. Physiologically active process, less commonly induced by RT.

Question 8

Time frame for Mitotic catastrophe

Answer 8

hours - days since cells have to go through the cycle

Question 9

Necroptosis requires what protein?

Answer 9

Regulated necrosis. RIPk1/RIPk3, induced by cell death receptors. Lacks caspase activation.

Question 10

Ferroptosis

Answer 10

iron-dependent non-apoptotic regulated cell death induced by lipid peroxidation.

Question 11

PCR of apoptosis vs mitotic catastrophe

Answer 11

apoptosis is a ladder, mitotic catastrophe is a smear

Question 12

Inhibitors of apoptosis

Answer 12

Survivin, XIAP

Question 13

Role of SMAC/DIABLE in apoptosis

Answer 13

Downregulate apoptosis inhibitors

Question 14

Assays for apoptosis

Answer 14

TUNEL (uses TdT to transfer biotin-dUTP to strand breaks of cleaved DNA)
DNA Ladder formation (gel electrophoresis)
Annexin V labeling (most common, flow cytometry, detects phosphatydyl serase on the membrane prior to DNA cleavage)
DAPI - DNA specific flourescent dye

Question 15

What happens in the execution phase of apoptosis?

Answer 15

Nucleases cleave DNA into 180-200 base pair increments

Question 16

TNFR protein family is involved with what?

Answer 16

The extrinsic apoptosis pathway

Question 17

Bcl-xL inhibition of apoptosis takes place where?

Answer 17

mitochondrion

Question 18

Beclin is involved with what cell death process?

Answer 18

Autophagy

Question 19

What paracrine signal from apoptosis stimulates proliferation in other cells?

Answer 19

Caspase 3

Question 20

In the jejunum, are crypt stem cells morphologically different from differentiated cells?

Answer 20

no, but they proliferate 3-4 days after RT so you can check regrowth

Question 21

Till & McCulloch’s studies of RT response in murine heme colony forming units represent the first

Answer 21

demonstration of the presence of rare, pluripotent stem cells in normal tissue

Question 22

D(0) is also called the

Answer 22

mean lethal dose

Question 23

Equation relating mean lethal dose D(0), N, and Dq

Answer 23

ln(N) = Dq/D(0)

Question 24

D(0) definition

Answer 24

dose required to reduce the population of cells by a factor of 0.37.
Sometimes it is easier to use the dose required to reduce the population by a factor of 10 (0.1 to 0.01 etc) instead of D(0). D10 = D(0) ln10

Question 25

Tumor Control Equation

Answer 25

TCP = e ^(SF*M)

Question 26

90% cure is _____ surviving cells

Answer 26

0.105 surviving cells

Question 27

61% cure is _____ surviving cells

Answer 27

0.5

Question 28

50% cure is _____ surviving cells

Answer 28

.693

Question 29

37% cure is _____ surviving cells

Answer 29

1

Question 30

10% cure is _____ surviving cells

Answer 30

2.3

Question 31

Average number of surviving cells equation

Answer 31

N = SF * M

Question 32

% cure equation

Answer 32

TCP = e ^n (n= number of surviving cells)

Question 33

When given the D0 in a cell survival problem, what steps can you take to solve for total dose?

Answer 33

1) find number of log kills
2) find D10 of dose for 1 decade of log kills D10 = 2.3* D0
3) D10 * n log kills = total dose

Question 34

SF2

Answer 34

surviving fraction after 2 Gy

Question 35

e^(-1)

Answer 35

0.37

Question 36

D0 of most mammalian cells

Answer 36

1-2 Gy

Question 37

If N = 1 then the curve is

Answer 37

exponential (appears straight on the log graph)

Question 38

B= 0 means that…

Answer 38

All sublethal damage has been repaired

Question 39

Tumor regrowth assay

Answer 39

measures the time it takes for a tumor (in a mouse) to grow to a pre-determined size compared to controls

Question 40

Ras-Raf Mek ERK/MAPK leads to

Answer 40

cell proliferation

Question 41

Ras PI3K Akt mTOR pathway leads to

Answer 41

protein synthesis

Question 42

Ras Raf Mek ERK Msk1

Answer 42

Chromatin modeling

Question 43

Ras pathway with Jnk/Sek-1 leads to

Answer 43

Apoptosis