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Radiation Biology > Hall 3 - Cell Survival Curves > Flashcards

Hall 3 - Cell Survival Curves Flashcards

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1
Q

What is plating efficiency?

A

(Colonies counted / cells seeded) x 100%

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2
Q

What is the surviving fraction?

A

Cells that survive after RT normalized by plating efficiency

(Colonies counted / cells seeded) / (PE/100)

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3
Q

What is tumor control probability?

A

e^-n

n: avg number of surviving cells in tumor

*37% TCP requires reduction to average of 1 surviving cell

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4
Q

How many cells in 1 gram of tumor?

A

10^9

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5
Q

What is a log-linear survival curve?

A

Dose plotted on a linear scale
Surviving fraction on a logarithmic scale

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6
Q

At low doses for low LET radiation, the survival curve starts out _____ then _____.

A

straight, curves downward at higher doses

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7
Q

For high LET radiation, survival is ______.

A

Linear

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8
Q

When is the single-hit, single target model applied?

A

High LET
M phase
Cells without DNA repair

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9
Q

What are the two assumptions of the single-hit, multi-target model?

A
  1. Each cell contains n targets, all of which must be inactivated for cell kill
  2. Each target can be inactivated by passage of a charged particle (a hit)

*Now mostly replaced by linear-quadratic model

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10
Q

For the single-hit, multi-target model, what are D1 and D0? When there is one hit per target, what is the surviving fraction?

A

D1 = single-event killing (initial slope)
D0 = multiple-event killing (final slope)

Surviving fraction = 0.37 of initial value = 1/e

SF = 1 - [1 - e^(-D/D0)] ^n

D10 = dose to reduce the surviving fraction to 0.10 = 2.3 x D0

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11
Q

What is the extrapolation number (n) in the single-hit, multi-target model?

A

Where D0 intercepts y-axis
Number of targets per cell

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12
Q

What is Dq in the single-hit, multi-target model?

A

Quasithreshold dose
Where D0 intercepts x-axis
Theoretical dose below which radiation produces no effect

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13
Q

How is irreparable damage represented in the linear-quadratic model?

A

alpha x D

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14
Q

How is repairable damage represented in the linear-quadratic model?

A

beta x D^2

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15
Q

When are irreparable and repairable killing equal?

A

When D = alpha/beta

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16
Q

What is it called when cells not directly irradiated can be affected by nearby irradiated cells?

A

Bystander effect

17
Q

In apoptosis, what recruits phagocytes to engulf dying cells?

A

Phosphatidylserine

*Does not trigger inflammation

18
Q

Apoptosis does/does not correlate strongly with radiosensitivity?

A

Does

19
Q

What part of the linear-quadratic model represents apoptosis?

A

Alpha (linear/shoulderless)

*No dose rate effect

20
Q

What caspases are involved in the extrinsic apoptotic pathway?

A

8 and 10

Bind death ligands (FasL, TNF-alpha, TRAIL) to cell surface receptors

*8 can cleave Bid and activate the intrinsic pathway

21
Q

What is the surviving fraction in the linear quadratic model?

A

SF = e ^ -(aD + bD^2)

22
Q

What is the adapter protein in the intrinsic apoptotic pathway? What caspase does it affect?

A

Apaf-1
9

DNA damage&raquo_space; ATM/p53&raquo_space; pro-apoptosis (Bax, Bak, Bid, Bim, Puma, Nova) outbalance anti-apoptosis (Bcl-2, Bcl-xl, Mcl-l)&raquo_space; cytochrome c&raquo_space; complexes with Apaf-1&raquo_space; caspase 9

23
Q

What are the initiator caspases?

A

2, 8, 9, 10

24
Q

What are the effector caspases?

A

3, 6, 7

25
Q

What inhibits the effector caspases?

A

X-linked inhibitor of apoptosis (XIAP)

26
Q

What is DIABLO?

A

A pro-apoptotic protein that frees caspases to initiate apoptosis

27
Q

What is the alternative pathway to activate apoptosis?

A

Acid sphingomyelinase (ASMase)

Increased after RT&raquo_space; converts sphingomyelin to ceramide&raquo_space; activates intracellular caspase cascade in endothelial and tumor cells

28
Q

What do TUNEL, DNA laddering on gel, and annexin V staining assay for?

A

Apoptosis

29
Q

Does necrosis require ATP?

A

No, passive process

*Inflammatory (cell swells)

30
Q

What is the most common form of cell death from radiation?

A

Mitotic catastrophe (mitotic cell death)

*Multinucleated giant cells possible

31
Q

What does the survival curve look like in mitotic death-dominant cells?

A

Broad shoulder
Linear-quadratic function of dose
Dose-rate effect

32
Q

What initiates the formation of autophagosomes?

A

BECLIN-1

33
Q

What protein does autophagy require? Is it reversible?

A

ATG protein family

Yes

Selective if targeted to specific proteins or organelles (nonselective if bulky)

34
Q

What three things can trigger senescence?

A
  1. Telomere shortening
  2. Oncogene activation
  3. Radiation (DNA damage)
35
Q

What mediates senescence?

A

p53/Rb activation
Cip/Kip or INK4 proteins

*Elevated levels of cell cycle inhibitors (p16-INK4a, p21/Cip1)

Radiation Biology (29 decks)

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