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Rad Onc > Radiobiology > Flashcards

Radiobiology Flashcards

1
Q

Which of the DNA bases are single-ring (pyrimidine) and which are double-ring (purine)?

A 
Pyrimidine = thymine & cytosine
Purine = adenine & guanine
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2
Q

What is the D0 dose?

A

The dose of radiation that induces an average of one lethal event per cell, leaving 37% still viable

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3
Q

Why is DNA in cells more resistant to radiation damage than free DNA?

A
  • presence of molecular scavengers

- physical protection via protein (histone) packaging

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4
Q

What do nuclear foci of phosphorylated 53BP1 indicate?

A

DNA DSB

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5
Q

What is the extrapolation number, n? What type of curve results if n is large?

A

n is a measure of shoulder width

if n is large, the survival curve has a broad shoulder

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6
Q

Which genes appear to be responsible for induction of senescence?

A

Rb, p53

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7
Q

Following radiation, one cell line shows clear DNA laddering on electrophoresis, while another shows little evidence of DNA laddering. Which of these is more likely radiosensitive?

A

cell line with laddering –> indicates apoptosis

this is likely the more radiosensitive cell line

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8
Q

What is the OER for protons?

A

2.5-3.0

equivalent to x-rays

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9
Q

What is the average LET during the entrance plateau for protons? during the Bragg peak?

A

entrance: 0.5keV/um

Bragg peak: 100keV/um

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10
Q

The probability of which type of effect increases with radiation dose: deterministic or stochastic?

A

Both

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11
Q

What type of effect has a practical threshold dose and increases in severity with dose: deterministic or stochastic?

A

Deterministic

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12
Q

Which type of effect is best described as “random”, with no threshold observed and no change in severity with dose: What type of effect has a practical threshold dose and increases in severity with dose: deterministic or stochastic?

A

Stochastic

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13
Q

Which radiation-induced malignancy has the shortest latent period?

A

Leukemia

Peak incidence at 5-7 years

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14
Q

T/F: Radiation-induced solid tumors occur in younger patients than spontaneous tumors.

A

FALSE
Radiation-induced solid tumors tend to be expressed later in life, at the same time as spontaneous tumors of the same type

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15
Q

Which of the following risk models for malignancy following radiation exposure is favored by the BEIR committee:
absolute risk model
relative risk model
time-dependent risk model

A

Time-dependent risk model

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16
Q

Name the two international committees on radiation protection.

A

UNSCEAR - United Nations Scientific Committee on the Effects of Atomic Radiation (scholarly)
ICRP - Int’l Council on Radiological Protection

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17
Q

Name the two US committees on radiation protection.

A

BEIR - Biological Effects of Ionizing Radiation (US Nat’l Academy of Sciences)
NCRP - Nat’l Council on Radiological Protection and measurement
`

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18
Q

T/F: The incidence of CLL increases following radiation.

A

False - AML/CML account for most of the increase

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19
Q

The incidence of which types of leukemia increases most after radiation of a human population?

A

AML and CML

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20
Q

Which populations are most susceptible to increased incidence of ALL and stem cell leukemia following radiation?

A

Children

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21
Q

Which type of cancer has the highest relative risk of any malignancy following radiation of a population?

A

Leukemia (specifically AML, CML)

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22
Q

The risk of leukemia rises in a dose-dependent manner up to what dose?

A

3 Sv

Risk per unit dose at 1 Sv is about 3X greater than 0.1 Sv

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23
Q

Which population is most sensitive to induction of thyroid carcinoma following radiation?

A

Children

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24
Q

What is the threshold dose to the developing fetus for radiation-induced mental retardation?

A

0.3Gy

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25
Q

What is the unit for absorbed dose (J/kg)?

A

Gy

1 Gy = 100 rad

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26
Q

What dose rate defines high dose rate brachytherapy?

A

HDR is >12Gy/h

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27
Q

What dose rate defines low dose rate brachytherapy?

A

LDR brachytherapy is ~2Gy/hr

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28
Q

At what timeframe following RT to the globe is retinal hemorrhage and degeneration expected?

A

3-6 months

These lesions progress over time

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29
Q

How much energy is dissipated per ionization event in ionizing radiation?

A

33eV

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30
Q

What is the velocity (c) of electromagnetic radiation?

A

3x10^10 cm/s (3x10^8 m/s)

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31
Q

All forms of electromagnetic have the same velocity (c = 3x10^8 m/s) but differ in frequency (v) and wavelength. How can frequency be used to determine photon energy?

A

Photon energy = hv

…where h= Planck’s constant, 6.626E-34 J-sec

c= frequency (v) x wavelength (lambda)

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32
Q

What happens to the energy of electromagnetic radiation as the wavelength increases

A

Energy DECREASES as wavelength increases

c = frequency x wavelength

frequency @ energy (E = hv, where h = Planck’s constant)

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33
Q

What is the minimum energy of ionizing radiation

A

124 eV

wavelength <10E-6 cm

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34
Q

Which forms of particulate radiation have a net + charge?

A

protons, a-particles, heavy charged particles

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35
Q

Is electromagnetic radiation directly or indirectly ionizing?

A

indirectly –> gives up energy in the absorbing material to result in fast-moving charged particles

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36
Q

What is the kinetic energy of an electron liberated by an incident photon in the photoelectric process?

A

in photoelectric process, all energy from incident photon is given up to electron

kinetic E = hv - (electron binding E)

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37
Q

What is the primary free radical formed by indirect action of radiation?

A

H2O+ –> OH* + H3O

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38
Q

Which DNA molecules are single-ringed?

A

Pyrimidines (thymine, cytosine)

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39
Q

Which DNA molecules are double-ringed?

A

Purines (adenine, guanine)

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40
Q

What is D0? What proportion of cells are left viable after irradiation with this dose?

A

Dose that results in average 1 lethal event/cell

Leaves 37% viability

~2-3Gy for mammalian cells

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41
Q

About 95% of energy deposition events for x-rays are spurs. What is the energy & diameter of this event size, and how many ion pairs does it produce?

A

Spurs <100eV
4nm diameter
~3 ion pairs

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42
Q

Blobs are energy deposition events in the 100-500eV range. Which type of radiation produces blobs most commonly?

A

densely ionizing radiation (ie neutrons, a-particles)
7nm diameter
avg 12 ion pairs

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43
Q

What is gH2AX?

A

gH2AX is the phosphorylated form of histone protein H2AX

H2AX is rapidly phosphorylated in response to damage and accumulates at sites of DNA damage

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44
Q

What is 53BP1?

A

53BP1 is a nuclear protein that becomes phosphorylated in response to stress, forming nuclear foci at the site of DNA DSBs

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45
Q

How many bases are removed by base excision repair?

A

single base

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46
Q

T/F: defects in base excision repair (BER) lead to enhanced radiosensitivity.

A

FALSE

Defects in BER lead to increased mutation rate but NOT increased radiosensitivity

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47
Q

Which enzymes are involved in base excision repair?

A

DNA ligase
APE1
DNA-polB

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48
Q

What is xeroderma pigmentosum? Does this disorder result in increased radiosensitivity?

A

XP is a defect in nucleotide excision repair

Does NOT result in increased radiosensitivity but does enhance sensitivity to UV-induced damage

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49
Q

At what phase of the cell cycle does homologous recombination repair occur?

A

Late S/G2 (requires sister chromatid template)

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50
Q

ATM, Rad51, and BRCA1/2 are involved in what type of DNA repair?

A

Homologous recombination

Recruited to sites of DSB

ATM also involved in NHEJ

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51
Q

T/F: Defects in HRR and NHEJ results in increased radiosensitivity

A

TRUE

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52
Q

Defects in which DNA repair process result in microsatellite instability?

A

Mismatch repair

Ex: hereditary nonpolyposis colon cancer

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53
Q

Radiation exposure during which cell cycle phase results in chromosome aberrations?

A

Interphase –> prior to DNA duplication

Ex: dicentric, ring, symmetric translocation, small deletions

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54
Q

Radiation exposure after late interphase results in what type of aberration?

A

Chromatic aberration (break in single chromatid arm)

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55
Q

Which chromosomal aberrations are lethal?

A

Dicentric
Ring

ChromaTID lethal aberration = anaphase bridge

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56
Q

Which chromatid aberrations are lethal?

A

Anaphase bridge

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57
Q

What is the difference in dose required to produce reproductive death vs functional cell death?

A

loss of function ~100Gy

loss of replicative capacity ~2Gy

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58
Q

T/F: Cell survival curves assess cell death following radiation.

A

FALSE: Survival curves assess loss of replicative capacity, clonogenic cells = “survivors”

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59
Q

What is the plating efficiency?

A

colonies/# seeded x100

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60
Q

How is the surviving fraction calculated for a cell survival curve?

A 
# colonies/
#seeded * plating efficiency/100
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61
Q

What differentiates the slope of survival curves for high LET vs low LET radiation?

A

low LET - survival curve is log-linear at low dose (a component), exponential at mid-range doses (B component), and log-linear again at higher doses (a=B)

high LET - survival curve is log-linear at all doses; survival fraction is an exponential function of dose

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62
Q

In the linear quadratic model, what equation describes survival? What about the curve predicted by this equation does not correspond with clinical observation?

A

S = e^(-aD-Bd^2)

resulting survival curve is constantly bending; does not account for final log-linear portion

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63
Q

What is the cost common form of cell death following radiation?

A

mitotic cell death

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64
Q

What are the morphologic hallmarks of apoptotic cell death?

A

condensation of nuclear chromatin into crescents around the periphery, eventual cell separation into membrane-bound apoptotic bodies

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65
Q

T/F: Bcl-2 suppresses apoptotic cell death.

A

TRUE

Apoptotic cell death following RT is p53-dependent and suppressed by Bcl-2

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66
Q

Cellular senescence is an irreversible cell cycle arrest characterized by induction of which proteins?

A

p53

Rb

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67
Q

T/F - D0 for cells derived from patients with ataxia telangiectasia is less than for normal mammalian cells.

A

TRUE

D0 for normal cells ~1-2Gy, for AT cells ~0.5Gy

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68
Q

Which phase of the cell cycle varies most in the amount of time required?

A

G1

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69
Q

Which component of the a/B model is directly proportional to dose? What does this represent?

A

a = component proportional to dose

represents single-event killing

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70
Q

What component of the a/B model results from multiple-event cell kill? How does this component relate to dose?

A

B - exponential function of dose (D^2)

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71
Q

What is D10 in cell survival curves

A

Dose required to kill 90% of cells

D10=2.3XD0

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72
Q

What is the x-ray transition point?

A

midpoint of G2 where radiosensitivity shifts from markedly radioresistant (early G2) to radiosensitive (late G2)

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73
Q

During which phase of the cell cycle does radiosensitivity shift from highly radioresistant to highly sensitive?

A

G2

early G2 –> ver resistant
late G2 –> very sensitive

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74
Q

OER varies between cell cycle phases. What is the OER in early G2 vs S?

A

G2 - 2.3-2.4

S - 2.8-2.9

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75
Q

In which cell cycle phase do irradiated cells tend to arrest?

A

G2

allows for chromosomal damage repair prior to mitosis

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76
Q

Under which conditions is potentially lethal damage (PLD) most likely to be repaired?

A

post-radiation conditions suboptimal for growth

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77
Q

What is the difference between sublethal damage and potentially lethal damage? Which is more likely to be repaired?

A

SLD - can be repaired under normal circumstances (more likely to be repaired)

PLD - can be modified by environmental conditions post-radiation (ie suboptimal growth conditions –> PLD repair)

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78
Q

What effect does sublethal damage (SLD) repair have on the survival curve?

A

correlates with width of the shoulder region

better SLD repair –> wider shoulder

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79
Q

Sublethal damage is primarily what DNA lesion? What impact does dose fractionation have on repair?

A

SLD ~~ DSB

SLD repair = repair of DSB before they can interact to form lethal aberrations

Fractionation –> DSBs produced by the first dose may be repaired by the time the second dose is delivered

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80
Q

Is SLD repair more likely to occur with low-LET or high-LET radiation?

A

low-LET

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81
Q

What is the dose-rate effect?

A

As dose rate is lowered and exposure time is extended, biologic effect of a given dose is reduced

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82
Q

What impact does reduction of dose rate have on the survival curve?

A

Curve becomes shallower, shoulder disappears

83
Q

What is the average photon energy and half life of iridium-192?

A

130 keV

74.2 d

84
Q

What is the HVL (mmPb) for Ir-192?

A

2.5

85
Q

What is the HVL (mmPb) for cesium-137?

A

5.5

86
Q

What is the OER (range) for high-dose X-rays?

A

2.5-3.5

87
Q

What is the OER for densely ionizing high LET radiation such as a-particles?

A

There is no OER, there is no shoulder!

88
Q

What is the OER for neutrons?

A

~1.6 - falls between x-rays (2.5-3.5) and high LET (no OER)

89
Q

What is the mechanism of the OER?

A

Under hypoxia, DNA is chemically restored by reaction with sulfhydryl (SH) molecules
When O2 is present, formation of peroxide groups results in non restorable damage

90
Q

What concentration of O2 is required to result in radiosensitivity ~half-way between 0-100%

A

0.5% O2 (3mmHg)

91
Q

What are the units for LET?

A

keV/um

92
Q

The classification of radiation as densely or sparsely ionizing refers to the spatial separation of ionization events. What happens to the LET of a given type of radiation as energy increases?

A

as energy increases, LET

DECREASES!!!

93
Q

How does fractionation affect RBE?

A

RBE is greater for a fractionated regimen than a single dose (ie more separation of curves) because RBE is larger with smaller doses

94
Q

How does SLD repair impact RBE?

A

Tissues with high capacity for SLD repair have a higher RBE because shoulder is larger

95
Q

What happens to RBE as LET increases 0-10keV/um?

A

RBE increases slowly

96
Q

What happens to RBE as LET increases 10-100keV/um?

A

increases rapidly

97
Q

What happens to RBE as LET increases >100keV/um?

A

RBE decreases >100keV/um

98
Q

Why is 100keV/um considered the optimal LET in terms of RBE?

A

average separation btw ionization events at 100keV/um is 2nm (20A), which corresponds to the diameter of the DNA double-helix

99
Q

Two types of radiation are compared, one with LET = 95keV/um and the other with LET = 150keV/um. Which has higher RBE?

A

95keV/um

RBE decreases >100keV/um

100
Q

At what LET does OER reach 0?

A

200keV/um

101
Q

What is the approximate OER for a radiation with LET = 200keV/um?

A

0

102
Q

What happens to OER as LET increases from 0-60keV/um?

A

OER slowly decreases

103
Q

1 Sv = ___rem

A

1 Sv = 100rem

104
Q

1Gy = ___rads

A

1Gy = 100 rads

105
Q

What are the stages of acute radiation syndrome?

A

Prodromal, latent, manifest illness

106
Q

At what dose does cerebrovascular syndrome occur? When does death occur?

A

~40-100Gy

Results in death in 24-48hrs

107
Q

Whole body exposures >___Gy are considered absolutely lethal.

A

> 10Gy - death is certain

108
Q

At what acute radiation dose does gastrointestinal syndrome occur? When does death occur?

A

> 10Gy

Death in 3-10d

109
Q

At what acute radiation dose does hematopoietic syndrome occur? When does death occur?

A

2.5-5Gy

Peak incidence of death @30d

110
Q

At what does range should bone marrow transplantation be considered following acute whole body radiation exposure?

A

8-10Gy

> 10Gy, death is inevitable because of GI death, below 8Gy the patient is likely to survive with antibiotics alone

111
Q

What is the excess risk of childhood malignancy following radiation to the fetus?

A

6% increase in risk per Gy

112
Q

Sulfhydryl compounds can act as radio protectors for what type of radiation?

A

Sparsely ionizing

113
Q

What feature of sulfhydryl compounds allows for facilitation of DNA repair?

A

Donation of H atom

114
Q

What limits the use of cysteine as a radioprotector?

A

causes nausea and vomiting at doses required for radioprotection

115
Q

What is the only FDA-aproved radioprotective drug?

A

Amifostine - may also reduce mutagenesis

116
Q

How is amifostine converted to its active metabolite?

A

dephosphorylation by alkphos (ALP)

then can readily enter cells, prior to depths does not penetrate cells well

117
Q

What dose is required to induce permanent sterility in males vs females?

A

Males –> 6Gy single dose; fractionated doses cause more gonadal damage than single dose (2.5-3Gy)

Females –> 12Gy prepuberty, 2Gy premenopausal

118
Q

What dose is required to induce oligospermia in males? Azoospermia and temporary sterility?

A
  1. 15Gy –> oligospermia

0. 5Gy –> azoospermia, temporary sterility after 6wk latent period

119
Q

What is the doubling dose (ie dose of radiation that doubles the baseline spontaneous mutation rate) to induce heritable effects in humans?

A

Doubling dose = 1Gy

120
Q

What is the rate of risk of a hereditary mutation at a population level?

A

0.2%/Sv

121
Q

What is the embryonic stage most sensitive to radiation? What is the threshold dose for death at this stage?

A

Preimplantation - most sensitive

Threshold dose = 100mGy (10cGy)

122
Q

What effect does radiation have on the fetus at 8-15 weeks gestation?

A

Mental retardation and microcephaly

123
Q

What is the does limit to the embryo following declaration of pregnancy?

A

0.5mSv/month

124
Q

What are the characteristics of a deterministic effect?

A

Threshold dose
Dose-related severity
Probability increases with dose

125
Q

Is tissue fibrosis deterministic or stochastic?

A

Deterministic

126
Q

What type of radiation induced malignancy has the shortest latent period?

A

Leukemia - 5-7yrs

127
Q

What types of leukemia are most commonly induced by radiation?

A

AML, CML

CKK does not appear to be affected by radiation

128
Q

At what age are humans most susceptible to thyroid cancer induction by RT?

A

childhood

129
Q

At what age are humans most susceptible to lung cancer induction by RT?

A

middle age

130
Q

Where are the dividing cells in the ocular lens?

A

Limited to pre-equatorial region of epithelium; progeny differentiate and migrate towards posterior pole

131
Q

What impact does dose have on the latent period to cataract formation?

A

Higher dose –> shorter latent period

132
Q

T/F: High LET radiation is more effective at cataract induction

A

True

133
Q

Can a cataract be definitively classified as radiation-induced?

A

No - but certain cataracts (ie nuclear cataracts) are NOT radiation induced

134
Q

What is the threshold dose for cataract formation?

A

2Gy

135
Q

What is the half-life of 64-Cu (used in Cu-ATSM imaging)?

A

12.7 hours

136
Q

Which radio tracers can be used to image for angiogenesis?

A

Galacto-RGD and Dimeric-RGD

137
Q

Which radio tracer can be used to assay vascular perfusion?

A

Cu-PTSM

138
Q

What is 18F-FLT used to image for?

A

cellular proliferation

139
Q

What is the half-life for 18F (ie 18F-FDG, 18F-FLT)?

A

109 min (1.83hrs)

140
Q

What is the formula for HU?

A

HU = 1000 x (u-u,water)/u,water

where u = x-ray absorption

141
Q

What is the HU of air?

A

-1000

142
Q

What is the HU of soft tissue?

A

0-100

143
Q

What is the HU of fat?

A

-100-0

144
Q

What is the HU of bone?

A

> 500

145
Q

How much iodine is required to produce a change of 100 HU (ie iodinated contrast agents)?

A

10mM

146
Q

What is the spatial resolution of PET?

A

4-6mm

147
Q

What is the amount of cosmic radiation experienced at sea level? How does this change as altitude increases?

A

0.26mSv at sea level

doubles for each 2000m increase in altitude

148
Q

What is the highest source of internal radiation?

A

Potassium-40 - ~0.2mSV/year

149
Q

Which national agencies have the ability to enforce laws regarding radiation protection?

A

Nuclear Regulatory Commission

EPA

150
Q

What is used to calculate the equivalent dose (Sv)?

A

absorbed dose (gy) x Wr

Wr = radiation weighting factor, takes into account dose rate and RBE

151
Q

What is the Wr of electrons?

A

1 (same as photons)

152
Q

What is the Wr of protons?

A

2

153
Q

What is the Wr of neutrons

A

Continuous curve depending on neutron energy

154
Q

What is the Wr of a-particles?

A

20

155
Q

What is the difference between equivalent dose and effective dose? What are the units?

A

Equivalent dose takes into account Wr based on type of radiation

Effective dose also takes into account the relative contribution of each tissue/organ to two total detriment

Units - Sv

156
Q

What is the committed equivalent dose?

A

equivalent dose integrated over 50yrs

157
Q

What is the cumulative lifetime occupational exposure limit recommended by the NCRP?

A

10mSv x age

158
Q

What is the annual occupational exposure limit recommended by the NCRP?

A

50mSv/yr

159
Q

What is the public effective dose limit recommended by the NCRP for continuous exposure? Infrequent exposure?

A

1mSv/yr frequent, 5mSv/yr infrequent

160
Q

What air concentration of radon results in a dose of 1mSv/yr to bronchial epithelium?

A

20Bq/m3

161
Q

What is the action level of radon?

A

148Bq/m3

162
Q

What is the formula for surviving fraction?

A 
# colonies/
#seeded * plating efficiency/100
163
Q

What is the tissue rescue unit?

A

The minimal # of functional subunits required to maintain tissue function

164
Q

What are Michalowski’s H- and F-type populations?

A

Heirarchical - ie consists of stem cells, maturing, and functional cells

Flexible - can be triggered to divide by damage

165
Q

Which interleukins are induced by radiation?

A

IL-1, IL-6

IL-1 is radioprotective in hematopoietic cells`

166
Q

Which cytokine is implicated in late complications of RT?

A

TNFa

167
Q

What is the transit time for an epidermal cell from basal layer to desquamation from surface?

A

14d

168
Q

Which type of lymphocyte is most radiosensitive?

A

B cells > T cells

169
Q

When is oral cavity desquamation expected? How does this compare to skin?

A

12d

Skin slightly longer - 14d

170
Q

At what timepoint following RT is villous atrophy observed in the bowel?

A

2-4d

171
Q

Which segment of bowel is most radiosensitive?

A

small bowel

rectal tolerance dose ~70Gy!

172
Q

During what time period does acute pneumonitis occur?

A

2-6mo

173
Q

What are the target cells for RT damage in lung?

A

endothelial cells

type II pneumocytes

174
Q

In the brain, which type of brain matter will show histopathologic change in the first year? After 12 mo?

A

First year –> white matter

>12mo –> gray

175
Q

There are two syndromes of late damage to the spinal cord following RT. What occurs between 6-18mo, and at 1-4 years?

A

6-18mo –> demyelination and white matter necrosis

1-4 years –> vasculopathy

176
Q

What is the target tissue underlying the 6hr separation of fractions?

A

CNS - sublethal damage repair is slow in CNS

177
Q

Which vascular structures are most radiosensitive? Least radiosensitive?

A

Capillaries - most radiosensitive
arteries - middle
veins - least radiosensitive

178
Q

At what point in the cell cycle is the cell committed to S phase, and no longer responding to growth signals?

A

G1 restriction point

regulated by Rb

179
Q

What is the most important cell cycle checkpoint following radiation damage?

A

G2/M

180
Q

What do Chk1 and Chk2 inhibit?

A

Chk1 –> inhibits Cdk1

Chk2 –> inhibits Cdk2

181
Q

Which cyclin do p53 and p21 inhibit?

A

Cyclin D/E

182
Q

What is the equation for mitotic index?

A

MI = 0.693 x Tm/Tc

Where Tm is length of mitosis and Tc is total length of cell cycle

183
Q

What is the equation for cell loss within a tumor population?

A

1 - Tpot/Td

where Tpot is potential tumor doubling time and Td is actual tumor doubling time

184
Q

In which type of solid tumor is apoptosis common?

A

Carcinoma

Apoptosis is rare in sarcomas

185
Q

What is the nominal standard dose?

A

total dose for tolerance of connective tissue as related to number of fractions (N) and overall time (T)

Total dose = (NSD)T^0.11N^0.24

186
Q

How do the dose-response curves for early and late responding tissues differ?

A

Curve is steeper/more curved for late responding tissues

187
Q

Can the bladder and kidneys be retreated following a first course of RT?

A

NO - bladder and kidney are not capable of recovery from late functional damage and do not tolerate retreatment

188
Q

BED calculations assume a 2Gy/fx schedule. What is the assumed a/B for early responding tissues? Late responding tissues?

A

Early responding tissues - a/B = 10

Late responding tissues - a/B = 3

189
Q

What is HIF1 & where is it expressed? Where is HIF2a expressed?

A

HIF1 = global regulator of hypoxia-inducible gene expression; expressed in most cell types

HIF2a = expressed primarily in endothelial cells, glial cells, type II pneumocytes, heart, kidney, pancreas, and liver

190
Q

How is HIF expression regulated?

A

In the presence of O2, HIF is hydroxylated by prolyl hydroxylases and ubiquitinated by VHL. Under hypoxia, PHD cannot hydroxylate HIF.

191
Q

How does HIF1a regulate gene expression?

A

Binds to HIF1B in the nucleus and promotes transcription of genes involved in angiogenesis (ie VEGF), erythropoiesis, and glycolysis

192
Q

What effect does mutation of VHL have on HIF?

A

HIF is stabilized in VHL-mutated individuals, as VHL usually targets HIF for destruction. VHL-mutated individuals are prone to development of highly vascularized tumors

193
Q

In addition to HIF, what cellular response can be induced in response to prolonged hypoxia?

A

Unfolded protein response (UPR)

194
Q

What is PERK?

A

PERK is a stress sensor in the ER involved in the Unfolded Protein Response pathway induced by hypoxia. PERK is important for surviving long term hypoxia.

195
Q

What is the dose limiting toxicity of misonidazole?

A

Neurotoxicity - peripheral and CNS

196
Q

Order the following drugs in terms of neurotoxicity:
Nimorazole
Etanidazole
Misonidazole

A

Misonidazole - most toxic
Etanidazole
Nimorazole - least toxic

197
Q

Which of the quinone antibiotics is recognized as a hypoxic cytotoxin?

A

Mitomycin C

198
Q

The efficacy of chemotherapy drugs is limited by the growth fraction of the tumor. What happens to the growth fraction as tumor size increases?

A

Growth fraction decreases as tumor size increases

199
Q

3 of the following drugs are preferentially toxic to aerobic cells. Which is preferentially toxic to hypoxic cells?

  • Bleomycin
  • Procarbazine
  • DOX
  • Actinomycin-D
A

Doxorubicin

Bleo, proverb, and dactinomycin are all preferentially toxic to oxygenated cells

200
Q

What impact does oxygenation have on cellular toxicity of 5-FU, methotrexate, cisplatin, and CCNU?

A

NONE

201
Q

What is the mechanism of cellular damage due to hyperthermia?

A

Protein denaturation

202
Q

Does hypoxia affect sensitivity to hyperthermia? What other factors impact sensitivity to hyperthermia?

A

Hypoxia - no

Factors that impact sensitivity:

  • changes in lipid component of cell membrane
  • acidic pH
  • nutritional deprivation
203
Q

How is hyperthermia measured?

A

Cumulative equivalent minutes (CEM)

ie measure of thermal dose CEM 43C T90 refers to the # of minutes 90% of the tumor was at 43C

204
Q

Following irradiation, cells tend to stall in the ___ phase of the cell cycle.

A

G2

Rad Onc (6 decks)

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