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
Q

The free radicals produced by ionizing radiation are _______, ________, _______, and _______.

A

ROS
RNS
RHS (reactive halogenated species)
prehydrated electron

26
Q

Transient generation of ROS/RNS/RHS has been detected within ________ of exposing the cell to IR.

A

minutes

27
Q

________ and ________ are the sources for ROS/RHS/RNS.

A

mitochondrion
cytoplasm

28
Q

__________ act as signaling molecules, ________ plays a role in immune defense.

A

ROS/RNS
RHS

29
Q

amount of ROS produced by IR at clinically relevant radiation doses is __________ then the background (endogenous) ROS level produced by _____________ of the cell.

A

1000 fold lower
oxidative metabolism

30
Q

The lethal radiation dose for a human body is _________.

A

4 Gy

31
Q

The unit _______ is use for radiation dose.

A

Gy

32
Q

A ________ measures the number of living cells. It is _______ and takes _________.

A

viability assay
quick
24-72 hours

33
Q

A __________ measures the number of clones produced by seeded cells. It is ________ and takes _________. It is __________.

A

clonogenic assay
more difficult to measure
1-2 weeks
more relevant to clinical treatment outcome

34
Q

A cell survival curve describes the relationship between ___________ and ___________.

A

radiation dose
proportion of cells that survive

35
Q

For differentiated cells that do not proliferate, death is ___________.

A

loss of a specific function

36
Q

For proliferating cells, death is __________.

A

loss of reproductive integrity.

37
Q

In radiobiology a cell is dead if it has lost the capacity to _________ and produce _____________.

A

divide indefinitely
large number of progeny

38
Q

A __________ retains its reproductive integrity and is able to proliferate indefinitely to produce a colony.

A

clonogenic cell

39
Q

For tumors, cells are dead if they are ________ and cause __________.

A

unable to divide
further growth/spread of malignancy

40
Q

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.

A

target theory

41
Q

D0 is the dose that gives an average of ____________, which corresponds to the dose to reduce the survival to _______. Also called _______.

A

1 hit/target
0.37
D37

42
Q

The D10 dose results in ____________. Also said to reduce survival by __________. The formula for D10 is:

A

one decade of cell killing
fraction of 10
D10 = ln10 x Do = 2.3 x D0

43
Q

The linear and quadratic contributions to cell killing are equal at a dose ____________.

A

equal to the ratio of alpha to beta

44
Q

__________ is the process of programmed cell death, characterized by stereotyped sequence of morphologic events.

A

apoptosis

45
Q

_________ is a form of traumatic cell destruction from acute cellular injury, culminating in the release of _____________.

A

necrosis
intracellular components

46
Q

___________ is when cell growth decelerates (after rapidly proliferation) and the cell enter permanent cell-cycle arrest.

A

senescence

47
Q

____________ is a mechanism where long-lived proteins and organelle compounds are directed to and degraded within ____________.

A

autophagy
lysosomes

48
Q

____________ is caused by _________ which does not produce proper chromosome segregation and cell division.

A

mitotic cell death
aberrant mitosis

49
Q

Death of the organism following lethal dose of radiation is caused by failure of _____________, particularly the ___________ and ____________, to repair damage.

A

a few sensitive tissues
hematopoietic system
epithelium of the small intestine

50
Q

Mode of cell death in normal tissue cells is ____________. Cells with high proliferative capacity tend to ___________. Cells with many fibroblasts tend to _________.

A

tissue specific
apoptosis
growth arrest

51
Q

Killing of tumor cells is less likely to occur because of __________ and more likely from ___________ or ____________ than the case for normal tissue.

A

apoptosis
mitotic catastrophe
senescence-like irreversible growth arrest

52
Q

Many tumors lose their ___________ mechanisms during progression.

A

pro-apoptotic

53
Q

Mitotic cell death is frequently followed by __________ in _________ cells.

A

apoptosis
apoptosis-competent

54
Q

The D0 of the effective survival curve requires a dose of ~ ________ for human cells, depending on the tumor type.

A

3 Gy

55
Q

D10 is the dose to kill ___________ of the population, given by ____________.

A

90%
D10 = 2.3 x D0