ASTRO Questions Flashcards
What is the approximate maximum diffusion distance of oxygen from a
normally-oxygenated capillary through a typical respiring tissue?
200 um (0.2 mm)
Modifiers of Cell Survival: Oxygen Effect
Estimate of hypoxic fraction?
surviving fraction hypoxic/surviving fraction oxygenated
Modifiers of Cell Survival: Oxygen Effect
What is Km for radiosensitivity?
Oxygen concentration 0.5-1% (3-8 mmHg)
The oxygen concentration at which cellular radiosensitivity is halfway between the fully aerobic and fully hypoxic response
Modifiers of Cell Survival: Oxygen Effect
The most dramatic change in radiation sensitivity occurs over which range of oxygen tension (in units of mm Hg or Torr)?
0-30 mm Hg (Torr).
Cells irradiated under an oxygen partial pressure at the low end of this range are maximally radioresistant, whereas irradiation at 30 mm Hg oxygen results in near maximum radiosensitization
Modifiers of Cell Survival: Oxygen Effect
Relationship between OER, LET and RBE?
When LET increases, OER decreases.
When LET increases, RBE increases until reaching a maximum at approximately 100 keV/µm, and then decreases.
Modifiers of Cell Survival: Oxygen Effect
OER values obtained for high energy protons used in radiotherapy are
similar to those measured for X-rays. True or false?
True
Since the high energy protons used in radiotherapy have an LET similar
to that of X-rays, their OER values are also similar.
Modifiers of Cell Survival: Oxygen Effect
What oxygen partial pressure is needed for full radiosensitization?
2-3%
Modifiers of Cell Survival: Oxygen Effect
What is OER?
The OER is defined as the ratio of the radiation dose needed to cause a
certain biological effect in hypoxic cells divided by the dose needed to
produce the same effect in aerated cells
Modifiers of Cell Survival: Oxygen Effect
Why the tumor is more radiosensitive in aerated conditions?
The increased cell killing resulting from irradiation in the presence of
oxygen is thought to be the result of increased radical damage and damage
fixation by oxygen. The initial number of ionizations produced by
radiation in the aerated and hypoxic cells would be the same
Modifiers of Cell Survival: Oxygen Effect
For single, large radiation doses delivered at a high dose rate, the ratio of
the OER for X-rays divided by the OER for 15-MeV neutrons is
approximately
2
Since the X-ray OER is typically about 3 and the OER for 15 MeV
neutrons is about 1.6, the ratio of the OERs is about 2
Modifiers of Cell Survival: Oxygen Effect
What does hypoxia do to gene transcription?
Exposure of cells to hypoxia, as in other stress situations, leads to changes
in expression of a number of stress genes, many of which are responsive
to the transcription factor, hypoxia-inducible factor-1a (HIF1A).
Modifiers of Cell Survival: Oxygen Effect
What is the primary mechanism that oxygen acts as a radiosensitizer?
through its ability to “fix” radiation-induced DNA damage
Modifiers of Cell Survival: Oxygen Effect
What are the processes that an incident photon can undergo based on its energy?
Photoelectric absorption: The photon’s energy is absorbed by an electron in the metal.
Compton scattering: The photon collides with a target at rest, and a new photon emerges at an angle. The target recoils, carrying away some of the incident energy.
Electron-positron pair production: The incident photon can undergo this process.
Radiation interaction with matter
What is the primary product of water radiolysis and how much of the indirect damage is attributed to it?
OH* (hydroxyl radical)
65-75%
Radiation interaction with matter
The approximate minimum photon energy required to cause ionization of
a water molecule is:
10-25 eV
On average, about 25 eV is required to create an ion pair in water,
although the minimum energy needed to eject an electron is only 12.6 eV
Radiation interaction with matter
Which of the following X-ray interactions with matter is most important
for producing high-contrast diagnostic radiographs?
Photoelectric effect
Radiation interaction with matter
What is the photon energy range for photoelectric, Compton, and triplet production?
100 KeV - Compton
10 KeV - photoelectric
1-2 MeV - triplet production
Radiation interaction with matter
The lifetime of an OH* radical is approximately:
10^-9 second
Radiation interaction with matter
Annihilation photons always have an energy of …. MeV each in pair production.
Annihilation photons always have an energy of 0.511 MeV each, which
is equal to the rest energy of the positron and electron.
Radiation interaction with matter
What results from the recombination of the initial water radiolysis products?
Water
Radiation of the pure water results in short-lived free radicals:
H2O -> OH (45%) + H(10%) + e-aq
These will react with DNA or each other
OH + H -> H2O
e-aq + e-aq +2 H2O -> H2 + 2 OH-
OH + OH -> H2O2
H + H -> H2
Radiation interaction with matter
Molecular mechanisms of DNA damage
For survival fraction of 37% (to kill 63% of cells), how many double strand breaks or pyrimidine dimers are needed?
40 DSBs
1,000,000 pyrimidine dimers
Molecular mechanisms of DNA damage
Which assay would be the most appropriate to use for quantitative measurement of DNA double-strand breaks (DSBs) in cells immediately following exposure to ionizing radiation?
Neutral comet assay
Molecular mechanisms of DNA damage
What does alkaline elution assay measure?
measure single-strand breaks and some base
damages
Molecular mechanisms of DNA damage
What does BrdU incorporation assay measure?
the amount of new DNA synthesis
Molecular mechanisms of DNA damage
Gamma-H2AX foci can be detected within ….. of
radiation exposure
15 mins
Molecular mechanisms of DNA damage
Which molecule has been shown to be a reliable surrogate marker
for DNA double strand breaks (DSBs) in the cells?
Phosphorylated histone variant H2AX (or gammaH2AX)
Molecular mechanisms of DNA damage
Double-strand DNA breaks caused by ionizing radiation trigger the
transcription of DNA damage response genes. Which of the following
proteins is a transcriptional transactivator?
A. p21 (CDKN1A)
B. p53 (TP53)
C. ATM
D. CHK1 (CHEK1)
E. TRAIL (TNFSF10)
p53
In response to various forms of DNA damage, including
double-strand breaks, p53 is stabilized and binds to the promoters of
numerous target genes, including p21, activating their transcription. This
transcriptional transactivation by p53 is an important component of the
cellular DNA damage response.
Molecular mechanisms of DNA repair
Molecular mechanisms of DNA repair
Which of the following proteins is most involved in homologous
recombinational repair of radiation-induced DNA double-strand breaks?
A. RAD51
B. XPG (ERCC5)
C. DNA-PKcs (PRKDC)
D. CHK1 (CHEK1)
E. TFIIH
RAD51
Molecular mechanisms of DNA repair
A mutation in which of the following genes is LEAST likely to cause an
increase in sensitivity to ionizing radiation:
A. NBS1(NBN)
B. BRCA1
C. ATM
D. MRE11
E. XPC
XPC is a gene whose product is involved in nucleotide excision repair
(NER). Mutations in XPC result in the human genetic disease xeroderma
pigmentosum, which is characterized by extreme sensitivity to ultraviolet
light. Mutations in all of the other genes result in human genetic diseases
characterized by sensitivity to ionizing radiation, including Nijmegen
breakage syndrome (NBS1), familial breast cancer (BRCA1), ataxia
telangiectasia (ATM), and ataxia telangiectasia-like disorder (MRE11).
Molecular mechanisms of DNA repair
Two of the main proteins involved in mismatch repair are:
MSH2/MLH1
Molecular mechanisms of DNA repair
What is the action of an exonuclease
enzyme?
Removes nucleotides from the ends of DNA strands
Molecular mechanisms of DNA repair
Defect in which one leads to more sensitivity to ionizing radiation? HR or NHEJ?
NHEJ
Cells with genetic defects in NHEJ (such as mutation of DNA-PK, XRCC4, or DNA ligase IV) display a more pronounced hypersensitivity to ionizing radiation than cells defective in HR (such as mutation of
BRCA1, BRCA2, or RAD51).
Molecular mechanisms of DNA repair
Chemotherapeutic agents frequently produce DNA double-strand breaks
(DSBs) by causing stalling and collapse of DNA replication forks. Which
of the following pathways has a dominant role in the repair of replicationassociated
double-strand breaks?
Homologous recombination (HR)
Molecular mechanisms of DNA repair
BRCA1 and BRCA2 predominantly regulate which type of DNA DSB repair?
BRCA1 and BRCA2 predominantly regulate homologous
recombination as opposed to non-homologous end joining
Molecular mechanisms of DNA repair
Molecular mechanisms of DNA repair
Molecular mechanisms of DNA repair
