Review Slides Part 1 Flashcards
Mammalian cells have specialized pathways to sense, respond to and repair _____________ such as ___________________.
specific damage formats
base damage, SSBs, DSBs, sugar damage, DNA-DNA and DNA-protein crosslinks
There are different repair pathways for repairing DNA damage depending on _____________.
stage of the cell cycle
Eukaryotic cell mechanisms to restore the structural integrity of DNA includes
1.
2.
3.
4.
5.
6.
- direct repair of defects
- nucleotide excision repair
- base excision repair
- mismatch repair
- homologous recombination
- non-homologous end-joining
Nucleotide excision repair (NER) fixes ___________ such as ___________ produced by UV irradiation.
bulky lesions
pyrimidine dimers
Base excision repair (BER) repairs __________ and __________.
damaged bases
SSBs
Mismatch repairs corrects ____________ and ________ as they occur during _________.
mismatched nucleotides
small loops
replication
Homologous recombination repairs ___________.
DSBs
Non-homologous end-joining repairs ___________.
DSBs
The types of lesions caused by ionizing radiation are _________, __________, _________, _________, __________, _________, and _________.
base damage
AP sites
SSBs
DSBs
dimers
bulky adducts
base mismatches
Disturbances in the normal redox state of tissues can cause toxic effects through the production of __________ and ________ that _________ of the cell.
peroxides
free radicals
damage all components
Oxidative stress is the imbalance between _____________ and a biological systems ability to _____________.
production of ROS
detoxify the ROS/repair the resulting damage
Some ROS can act as messengers through ____________.
redox signaling
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 __________.
disease
sickle cell, Parkinsons, heart failure, Alzheimer’s, bipolar, etc.
attacking and killing pathogens
immune system
Superoxide is produced in significant amounts ____________.
intracellularly
The major reactive oxygen species (ROS) are ________, _________, __________, ________, __________, and _________.
singlet oxygen
superoxide
hydrogen peroxide
hydroxyl radical
nitric oxide
HOCl/HOBr/HOI
_____________ is formed after absorption of energy.
Singlet oxygen
Superoxide comes from _____________ from electron transport; activated ____________; __________ and __________.
leakage of electrons
phagocytes
xanthine oxidase
flavoenzymes
Superoxide is ________ oxidizing, _________ reductive.
weakly
mostly
___________ has similar binding energy to pre-hydrated electron. They both cause __________ damage.
Superoxide
reductive
The enzyme defenses for superoxide is __________. The products are __________.
superoxide dismutase
H2O2 + O2
Hydrogen peroxide is _________ oxidizing.
weakly
___________ is produced from superoxide via SOD.
hydrogen peroxide
________ is the major target of ionizing radiation however more research is being conducted on contribution of __________ damage to cell death induced by radiation.
DNA
cytoplasm
Irradiation of the cytoplasm alters ___________ which might contribute to the activation of ___________ that could impact upon the damaging effects of radiation.
intracellular metabolic redox reactions
protective or damaging processes
The free radicals produced by ionizing radiation are _______, ________, _______, and _______.
ROS
RNS
RHS (reactive halogenated species)
prehydrated electron
Transient generation of ROS/RNS/RHS has been detected within ________ of exposing the cell to IR.
minutes
________ and ________ are the sources for ROS/RHS/RNS.
mitochondrion
cytoplasm
__________ act as signaling molecules, ________ plays a role in immune defense.
ROS/RNS
RHS
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
The lethal radiation dose for a human body is _________.
4 Gy
The unit _______ is use for radiation dose.
Gy
A ________ measures the number of living cells. It is _______ and takes _________.
viability assay
quick
24-72 hours
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
A cell survival curve describes the relationship between ___________ and ___________.
radiation dose
proportion of cells that survive
For differentiated cells that do not proliferate, death is ___________.
loss of a specific function
For proliferating cells, death is __________.
loss of reproductive integrity.
In radiobiology a cell is dead if it has lost the capacity to _________ and produce _____________.
divide indefinitely
large number of progeny
A __________ retains its reproductive integrity and is able to proliferate indefinitely to produce a colony.
clonogenic cell
For tumors, cells are dead if they are ________ and cause __________.
unable to divide
further growth/spread of malignancy
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
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
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
The linear and quadratic contributions to cell killing are equal at a dose ____________.
equal to the ratio of alpha to beta
__________ is the process of programmed cell death, characterized by stereotyped sequence of morphologic events.
apoptosis
_________ is a form of traumatic cell destruction from acute cellular injury, culminating in the release of _____________.
necrosis
intracellular components
___________ is when cell growth decelerates (after rapidly proliferation) and the cell enter permanent cell-cycle arrest.
senescence
____________ is a mechanism where long-lived proteins and organelle compounds are directed to and degraded within ____________.
autophagy
lysosomes
____________ is caused by _________ which does not produce proper chromosome segregation and cell division.
mitotic cell death
aberrant mitosis
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
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
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
Many tumors lose their ___________ mechanisms during progression.
pro-apoptotic
Mitotic cell death is frequently followed by __________ in _________ cells.
apoptosis
apoptosis-competent
The D0 of the effective survival curve requires a dose of ~ ________ for human cells, depending on the tumor type.
3 Gy
D10 is the dose to kill ___________ of the population, given by ____________.
90%
D10 = 2.3 x D0
