Ch 8 Tumor growth and responce Flashcards
Responce of organ/tissue depends on (3)
- Sensitivity of cell populations
- Type of cells/tissues that make up that organ
- Turnover kinetics of each
Rad. responce =
When and if cells divide
Bergonie and Tribondeau (1906)
Did experiments on rodent ___. Beacuse it contained both ___ and ___ cells.
- Testicles
- Mature and immature
Bergonie and Tribondeau (1906)
Stated the “cell divison was important to…”
selective cell killing”
Bergonie and Tribondeau (1906)
Stated that radiation sensitivity for alll cells in the body were based on…
Miotic activity and differentiation
Bergonie and Tribondeau (1906)
Ionizing radiation is more effective afainst cells that are A.U.H
- Actively dividing
- Undifferentiated
- Have a long dividing future
Bergonie and Tribondeau (1906)
Stated that the ___ of radiation damage differs among type of cells
Apperance
ANCEL AND VITEMBERGER
(1925)
The appearance of radiation damage is influenced by (2)
- Biological stress on the cell
- Pre and post irradiation conditions of the cell
ANCEL AND VITEMBERGER
(1925)
The greatest influence on radiosensitivity
is the
biologic stress placed on the cell (division)
All cells are damaged to same degree.
___ is expressed if/when the cell
___
- Damage
- Divides
Cells dividing quickly express ___ sooner and appear more ___
- Damage
- Sensitive
ANCEL AND VITEMBERGER
(1925)
All cells are ___ sensitive, just rapidly dividing cells show ___ faster because it is expressed during ___
- Equally
- Damage
- Division
What is important when evaluating radiosensitivity of tissue (3)
- Cell division
- Turnover
- Kinetics
Differentiation of a cell determines the degree of (3)
- Functional specialization
- Morphological specialization
- Maturity
Undifferentiated immature cells primary function is to ___ and replace ___ cells
- Divide
- mature
Undifferentiated immature cells aka (2)
- Precursor
- Stem cells
Cell Populations names
- Stem cells
- Transit cells
- Static cells
- Primitve
- Transforming
- Not changing / Finalized
___ - divide/self renewal and maintain other cell populations
Stem Cell Population
___ - cells going from stem cell compartment to end cell compartment,
Transit Cell Population
Transit Cell Population examples (2)
- Nucleated
- Reticulocyte
___ - fully differentiated, exhibit little or nomitotic activity. Loses cells throughout life span. No replacement of cells.
Static population
Stem cells are differentiated or undifferentiated
Undiffentiated
Transit cells may or may not ___
Divide
Transit cells are neither ___ or ___
- Mature
- Immature
Static cells have little to no ___ ___
Miotic activity
Static cells are differentiated or un differentiated
differentiated
RUBIN AND CASARETT
Cell populations from most senstive to least (4)
- Vim
- Dim
- Mpc
- Rpm
- Fpm
Differentiation cell populations are (3)
- Stem
- Transit
- Static
Parenchymal Compartment contains the cells ___ of the ___ ___ or organ
- Characteristics
- individual tissue
Stromal Compartment contains ___, ___, ___ of the organ
- Connective tissue
- Vasculature
- Supporting stuctures
Tissue responce to Rad.. New hypothesis:
Response is due to killing and
subsequent depletion of the critical
___cells of the organ
- Parenchymal
Tissue responce to Rad.. New hypothesis:
Differences in the time it takes for
damage ___ due to differences
in ___ ___ of target
cells.
- Expression
- Turnover Kinetics
Damage to intestines
- Expressed in _ - _ weeks post irradiation
- ___ hour cell cycle of stem cells
- 1-2
- 12
Damage to lung
- Expressed in ___ months post irradiation
- Reflects a slower turnover of ___ cells
- 3
- Parenchymall
Normal tissue catagories are based on ___
Turnover Kinetic
Acutely responding normal tissue
- Manifest injury within a few ___ post Rx
- All are ___ ___ ___containing rapidly dividing stemm cell populations
- Months
- self renewal tissues
Acutely responding normal tissue examples (4)
- Bone marrow
- Skin
- Intestines
- Testis
Late responding normal tissue
- Do not express injury for at least ___ months
- Contain ___ ___ cell populations
- 3
- slowly dividing
Rapidly dividing, stem cell populations and quick side effects are ___ responding tissues
Acutely
Slowly divididng, static cells and show injury after 3 months are ___ responding tissues
Late
What is an assay?
Analysis or study used to asses tissue damage as a function of dose
What do assay results provide?
Cell survival or dose responce curves
Cell survival assessed as function of
___
Dose
Despite many tests, the most critical
test involves the ability of the stem
cell to retain ___ ___
reproductive integrity
Clonogenic assay’s
Survival curves of tissue containing
__ ___ that divide and form clones
in ___.
- Stem cells
- vivo
A Functional Assay is an assay of ___ rather than ___
- Function
- Survival
Functional assys are used for tissure that do not have ___ ___ ___
Clonogenic stem cells
Functional assys produce data ___ curves rather than ___ ___ curves
- Responce
- Cell survival
Functional assys allow comparison of ___ ___ to radiation
Tissue Responce
Acutely responding organs caused __ or ___ sooner than late responding organs
- Death
- Paralysis
What is LD 50
Lethal dose that kills 50% of the animals
Internal factors that effect radio sensitivity
___ vs __
___ vs ___
- Differentiated vs undifferentiated
- Acute vs late responding tissue
External factors effecting tissue radiosensitivity (3)
- physical factors
- Chemical factors
- Biological factors
Cell and tissue responce can be modified to (3)
- Diminish the responce (radioresistant)
- Enchance the responce (radiosensitive)
- Change time of responce
___ factors exert an influence on the cell’s response to ___ (Vitemberger)
- External
- Radiation
___ ___ curves are constructed to compare the effect on cell survival of ___ ___ and ___ ___ radiations.
- Cell survival
- high LET
- Low LET
Decrease in shoulder region is due to ___ LET
Higher
High LET provides ___ number of ___ per unit of travel.
- Larger
- Ionizations
High LET expels its ___ quickly, but does not ___ ___
- Energy
- Travel Far
Define: Dose rate
The rate at which radiation is delivered. Gy per minute
Reducing dose rate on a survival curve makes the line more
Shallow / Flat
Low dose rates allow for cell ___
Repair
Reduction in DR causes shoulder on survival curve to ___
Broaden (Larger)
Which radiosensitizer has the most dramatic effect
Oxygen
The Oxygen Effect
Enhances formation of ___ ___ during ___ action with ___ content of cell
- Free radicals
- Indirect
- water
The Oxygen Effect blocks waht process of the cell
Restoration
The Oxygen Effect Draws ___ ___ into ___ ___ producing ___ damage
- Free radicals
- longer chains
- irreversible
The Oxygen Effect does not correct the damage, instead it aims to
fix the damage
Aerated cells graph characteistics:
- Slope shoulder region
- Slope (line)
- Smaller shouldler region
- Steeper
The Oxygen Effect maximum sensitivity is __mmHg, aka (oxygen tension)
30
The Oxygen Enhancement Ratio “Function” compares…
The responce of cells or organisms to radiaiton with and without radiation
OER equation is
Hypoxic / Oxygenated
Ex. 3/1 = 3 times more senstive under oxygenated conditions
OER for mammalinc cells is
2-3
OER is more pronounced with ___ LET
Low
Hight LET radiation ionizes so densely that targets are hit ___ ___ regardless of ___ ___ or O2 enhancement
- Multiple times (high cell kill)
- dose rate
What substitutes the base
of Thymidine in DNA
Halogen Pyrimidines
Halogen Pyrimidines changes ___ molecule making it more ___ te rad damage
- DNA
- Susceptible
Other rad sensitizers (4)
- Methotrexate
- Actinomycin D
- Hydroxyurea
- Vitamin K
The ___ group are known as radioprotectors
Sulfhydryl
Most radiosensitve cell phase
G2 – M
Most radioresistant cell phase
S
___ ___ affect cells in the most radiosensitive phases of the cell cycle, ___ their progression through mitosis
- low doses
- Delaying
At 3 Gy you produce ___ death
reporductive
CELL DEATH OCCURS AFTER ___
DIVISION
