Review Slides Part 1 Flashcards

1
Q

Mammalian cells have specialized pathways to sense, respond to and repair _____________ such as ___________________.

A

specific damage formats
base damage, SSBs, DSBs, sugar damage, DNA-DNA and DNA-protein crosslinks

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2
Q

There are different repair pathways for repairing DNA damage depending on _____________.

A

stage of the cell cycle

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3
Q

Eukaryotic cell mechanisms to restore the structural integrity of DNA includes
1.
2.
3.
4.
5.
6.

A
  1. direct repair of defects
  2. nucleotide excision repair
  3. base excision repair
  4. mismatch repair
  5. homologous recombination
  6. non-homologous end-joining
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4
Q

Nucleotide excision repair (NER) fixes ___________ such as ___________ produced by UV irradiation.

A

bulky lesions
pyrimidine dimers

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5
Q

Base excision repair (BER) repairs __________ and __________.

A

damaged bases
SSBs

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6
Q

Mismatch repairs corrects ____________ and ________ as they occur during _________.

A

mismatched nucleotides
small loops
replication

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7
Q

Homologous recombination repairs ___________.

A

DSBs

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8
Q

Non-homologous end-joining repairs ___________.

A

DSBs

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9
Q

The types of lesions caused by ionizing radiation are _________, __________, _________, _________, __________, _________, and _________.

A

base damage
AP sites
SSBs
DSBs
dimers
bulky adducts
base mismatches

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10
Q

Disturbances in the normal redox state of tissues can cause toxic effects through the production of __________ and ________ that _________ of the cell.

A

peroxides
free radicals
damage all components

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11
Q

Oxidative stress is the imbalance between _____________ and a biological systems ability to _____________.

A

production of ROS
detoxify the ROS/repair the resulting damage

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12
Q

Some ROS can act as messengers through ____________.

A

redox signaling

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13
Q

Oxidative stress in humans can be negative as it is involved in ___________ such as _____________. However it can also be positive in that they are used for __________ by __________.

A

disease
sickle cell, Parkinsons, heart failure, Alzheimer’s, bipolar, etc.
attacking and killing pathogens
immune system

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14
Q

Superoxide is produced in significant amounts ____________.

A

intracellularly

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15
Q

The major reactive oxygen species (ROS) are ________, _________, __________, ________, __________, and _________.

A

singlet oxygen
superoxide
hydrogen peroxide
hydroxyl radical
nitric oxide
HOCl/HOBr/HOI

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16
Q

_____________ is formed after absorption of energy.

A

Singlet oxygen

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17
Q

Superoxide comes from _____________ from electron transport; activated ____________; __________ and __________.

A

leakage of electrons
phagocytes
xanthine oxidase
flavoenzymes

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18
Q

Superoxide is ________ oxidizing, _________ reductive.

A

weakly
mostly

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19
Q

___________ has similar binding energy to pre-hydrated electron. They both cause __________ damage.

A

Superoxide
reductive

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20
Q

The enzyme defenses for superoxide is __________. The products are __________.

A

superoxide dismutase
H2O2 + O2

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21
Q

Hydrogen peroxide is _________ oxidizing.

A

weakly

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22
Q

___________ is produced from superoxide via SOD.

A

hydrogen peroxide

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23
Q

________ is the major target of ionizing radiation however more research is being conducted on contribution of __________ damage to cell death induced by radiation.

A

DNA
cytoplasm

24
Q

Irradiation of the cytoplasm alters ___________ which might contribute to the activation of ___________ that could impact upon the damaging effects of radiation.

A

intracellular metabolic redox reactions
protective or damaging processes

25
The free radicals produced by ionizing radiation are _______, ________, _______, and _______.
ROS RNS RHS (reactive halogenated species) prehydrated electron
26
Transient generation of ROS/RNS/RHS has been detected within ________ of exposing the cell to IR.
minutes
27
________ and ________ are the sources for ROS/RHS/RNS.
mitochondrion cytoplasm
28
__________ act as signaling molecules, ________ plays a role in immune defense.
ROS/RNS RHS
29
amount of ROS produced by IR at clinically relevant radiation doses is __________ then the background (endogenous) ROS level produced by _____________ of the cell.
1000 fold lower oxidative metabolism
30
The lethal radiation dose for a human body is _________.
4 Gy
31
The unit _______ is use for radiation dose.
Gy
32
A ________ measures the number of living cells. It is _______ and takes _________.
viability assay quick 24-72 hours
33
A __________ measures the number of clones produced by seeded cells. It is ________ and takes _________. It is __________.
clonogenic assay more difficult to measure 1-2 weeks more relevant to clinical treatment outcome
34
A cell survival curve describes the relationship between ___________ and ___________.
radiation dose proportion of cells that survive
35
For differentiated cells that do not proliferate, death is ___________.
loss of a specific function
36
For proliferating cells, death is __________.
loss of reproductive integrity.
37
In radiobiology a cell is dead if it has lost the capacity to _________ and produce _____________.
divide indefinitely large number of progeny
38
A __________ retains its reproductive integrity and is able to proliferate indefinitely to produce a colony.
clonogenic cell
39
For tumors, cells are dead if they are ________ and cause __________.
unable to divide further growth/spread of malignancy
40
The _________ model of cell survival is based on the concept that a number of critical targets have to be inactivated for cells to be killed.
target theory
41
D0 is the dose that gives an average of ____________, which corresponds to the dose to reduce the survival to _______. Also called _______.
1 hit/target 0.37 D37
42
The D10 dose results in ____________. Also said to reduce survival by __________. The formula for D10 is:
one decade of cell killing fraction of 10 D10 = ln10 x Do = 2.3 x D0
43
The linear and quadratic contributions to cell killing are equal at a dose ____________.
equal to the ratio of alpha to beta
44
__________ is the process of programmed cell death, characterized by stereotyped sequence of morphologic events.
apoptosis
45
_________ is a form of traumatic cell destruction from acute cellular injury, culminating in the release of _____________.
necrosis intracellular components
46
___________ is when cell growth decelerates (after rapidly proliferation) and the cell enter permanent cell-cycle arrest.
senescence
47
____________ is a mechanism where long-lived proteins and organelle compounds are directed to and degraded within ____________.
autophagy lysosomes
48
____________ is caused by _________ which does not produce proper chromosome segregation and cell division.
mitotic cell death aberrant mitosis
49
Death of the organism following lethal dose of radiation is caused by failure of _____________, particularly the ___________ and ____________, to repair damage.
a few sensitive tissues hematopoietic system epithelium of the small intestine
50
Mode of cell death in normal tissue cells is ____________. Cells with high proliferative capacity tend to ___________. Cells with many fibroblasts tend to _________.
tissue specific apoptosis growth arrest
51
Killing of tumor cells is less likely to occur because of __________ and more likely from ___________ or ____________ than the case for normal tissue.
apoptosis mitotic catastrophe senescence-like irreversible growth arrest
52
Many tumors lose their ___________ mechanisms during progression.
pro-apoptotic
53
Mitotic cell death is frequently followed by __________ in _________ cells.
apoptosis apoptosis-competent
54
The D0 of the effective survival curve requires a dose of ~ ________ for human cells, depending on the tumor type.
3 Gy
55
D10 is the dose to kill ___________ of the population, given by ____________.
90% D10 = 2.3 x D0