chapter 7 EXAM 3 Flashcards
what is the goal of radiobiologic research
the accurate description of the effects of radiation on humans so that radiation can be used more safely in diagnosis and more effectively in therapy
generalizations about radiation effects on living organisms #1
the interaction of radiation in cells is a probability function or a matter of chance
ionizing radiation does not seek out certain cells.
generalizations about radiation effects on living organisms #2
the initial deposition of energy occurs very rapidly
generalizations about radiation effects on living oragnisms #3
radiation interaction in a cell is nonselective
energy is deposited randomly
generalizations about radiation effects on living organisms #4
the visible changes in the cells, tissues and organs due to ionizing radiation are not unique. They can’t be distinguished from damage produced by other types of trauma
cancer is cancer
generalizations about radiation effects on living organisms #5
the biologic changes in cells and tissues resulting from radiation occur only after a period of time. The length of time depends on the initial dose and varies from weeks or even years
3 radiation energy transfer determinants
- Linear energy transfer (LET)
- relative biologic effectiveness (RBE)
- oxygen enhancement ratio (REO)
characteristics of ionizing radiation
charge
mass
energy
Linear Energy Transfer (LET)
the measure of the rate at which energy is transferred from ionizing radiation to soft tissue
LET is expressed in
kiloelectronvolts per micrometer
the LET of diagnostic xrays is
3 KeV/micrometer
considered Low LET
LET is a factor in
assessing potential tissue and organ damage from exposure to ionizing radiation
when LET increases,
the likelihood of biologic response increases
T or F
LET helps determine radiation weighting factors
true
radiation is divided into 2 categories according to LET
- low LET
2. high LET
Low LET
xrays and gamma rays
electromagnetic radiation is sparsely ionizing therefore it is Low LET
when interacting with biologic tissue Low LET causes damage primarily
through indirect action which involves the production of free radicals
free radicals
a solitary atom or a combo of atoms that behave as extremely reactive single entities as a result of the presence of an unpaired electron
Low LET radiation generally causes what kind of damage to the DNA
sublethal damage
repair enzymes revers the damage
direct action means
it will hit the nucleus of a cell
indirect action means
it will hit water
high LET includes
particles that possess large mass and charge
high LET causes
dense ionization along its length of track and more likely to interact with biologic tissue
way more destruction
examples of high LET radiation
alpha particles
ions of heavy nuclei
low energy neutrons
charged particles released from interactions between neutrons and atoms
T or F
high LET loses energy more rapidly than low LET
True
why does high LET lose energy more rapidly than low LET
high LET produces more ionization per unit of distance traveled
they exhaust their energy in a shorter length of track and cannot travel as far
the higher the LET the greater
the biologic response
relative biologic effectiveness definition
RBE
a term relating the ability of radiations with different LETs to produce a specific biologic response
RBE describes
the ratio of the dose of a reference radiation to a dose of radiation of the type in question that is necessary to produce the same biologic reaction in a given experiment
RBE =
dose in Gy from 250 kvp xrays / dose in Gy of test radiation
RBE is used to refer to
experiments with specific cells or animal tissues
RBE is not practical for
specifying radiation protection dose levels in humans
as LET increas so does
RBE
high LET radiations such as alpha partices has a high
RBE
low LET radiations such as xrays and gamma rays have a low
RBE
xrays have an RBE of
1
oxygen effect
biologic tissue is more sensitive to radiation when irradiated in an oxygenated (aerobic) state than when it is exposed to radiation under anoxic or hypoxic conditions
t or f
The oxygen enhancement ratio (OER) describes the oxygen effect numerically
true
Oxygen enhancement ratio (OER) definition
the ratio of dose required to produce a given biologic response in the absence of oxygen to the dose required to produce the same response in the presence of oxygen
OER =
dose necessary under anoxic conditions to produce a given effect / dose necessary under aerobic condtions to produce the same effect
xrays and gamma rays have an OER of what when radiation dose is high
3
when radiation doses are lower than 2 Gy the OER may be
less (about 2)
OER values for high let radiations are what and why
1
because the high LET radiations are so effective in producing damage, the presence or absence of oxygen doesn’t matter
radiation induced damage is observed on 3 levels
- molecular
- cellular
- organic
T or F
any visible radiation induced injuries to cells or the organism always begin with damage at the molecular level
true
molecular damage results in
the formation of structurally changed molecules that may impair cellular functioning
organic level:
when a sufficient number of somatic cells are affected,
the entire body processes could be adversely affected
organic level:
if germ cells are damaged,
the damage may be passed onto future generations in the form of genetic mutations
when ionizing radiation interacts with a cell,
ionizations and excitations are produced in vital macromolecules (such as DNA) or in the nedium in which the cellular organisms are suspended (water)
direct action (effect)
biologic damage occurs when any type of radiation ionizes master or key molecules such as DNA causing them to become inactive or functionally altered
what could the damages of direct action lead to
inappropriate chemical reactions
essential biochemical processes may not occur in the cell
indirect action (effect)
occurs when the radiation interacts with water in the cell causing the formation of free radicals
when the water molecule is irradiated through indirect action
a free radical is formed and can migrate tot eh master or key molecule (DNA) and can result in cell death
direct effect may result after exposure to…..
but is much more likely to happen after exposure to …
any type of radiation
high LET radiation than Low LET radiation
since the human body is 80% water and less than 1% DNA it’s assumed that
most of the effects of radiation in you result from the indirect effect
the primary mechanism for indirect action is
the radiolysis of water
radiolysis of water definition
when water is irradiated, it dissociates into other molecular products
for every molecule of DNA in the cell there are how many molecules or water
1.2 x 10^7
when a water molecule is irradiated it absorbs energy and dissociates into
a positive water ion and an electron
t or f
after the initial ionization of a water molecule, many reactions can happen
true
type of reaction that can happen from ionization of a water molecule
the ion pair AKA positive water molecule and electron may rejoin into a stable water molecule
no damage occurs
type of reaction that can happen from ionization of a water molecule
if the ions do not rejoin the electron can attach to another water molecule and produce another type of reaction (a negative water ion)
t or f
the HOH+ (positive water molecule) and the HOH- (negative water molecule) are unstable and can break apart into smaller molecules
true
HOH+ becomes
a hydrogen ion (H+) and a hydroxyl radical (OH+)
HOH- becomes
a hydroxyl ion (OH-) and a hydrogen radical (H*)
the ultimate result of the interaction of radiation with water is
the formation of an ion pair and 2 free radicals (H* and OH+)
the free radicals can also produce
other products that are poisonous to the cell and act as toxic agents
the OH+ (hydroxyl radical) can join with a similar molecule and form
hydrogen peroxide
toxic to the cell
can kill
the H* (hydrogen radical) can interact with molecular oxygen to form
hydroperoxyl radical
can kill the cell
free radicals are believed to be a major factor in
the production of damage via indirect action in the cell
2 points that are considered about the effects of radiation on DNA
- much of the damage in DNA can be, and is repaired by the cell
- all types of DNA damage are not equal in terms of their biologic significance
5 effects of ionizing radiation on DNA
- single strand break
- double strand break
- double strand break in the same rung of DNA
- mutation
- covalent cross links
single strand breaks (SSB)
the ionizaiton of a DNA macromolecule resulting in a break of one of its chemical bonds.
it severs one of the sugar phosphate chain side rails.
single strand break type of injury is also called a
point mutation
point mutations commonly occur with what kind of radiation
low LET radiation
can single strand breaks be repaired?
yes
repair enzymes can reverse the damage
no long term consequences to the cell
double strand breaks
ionization of a DNA macromolecule resulting in the rupture of one or more of its chemical bonds
creates one or more breaks in each of the 2 sugar phosphate chains
double strand breaks occur most commonly with what type of radiation
high LET radiation
can double strand breaks be repaired?
yes, but not as easily as SSB
double strand break in the same rung of DNA
if both strands of DNA are broken at the same nitrogenous base or rung resulting in complete breakage of DNA
can double strand breaks in the same rung of DNA be repaired ?
no it results in death or impaired functions of the new daughter cells
mutation
changes in genes caused by the loss or change of base in the DNA chain
mutation may not be
reversible and cause acute consequences for the cell
covalent cross links can occur in
many different patterns
all are potentially fatal to the cell if not properly repaired
intrastrand cross link
cross link formed between 2 places on the same DNA strand
interstrand cross link
cross link formed between complementary DNA strands or between entirely different DNA molecules
3 effects of ionizing radiation on chromosomes
- radiation induced chromosome breaks
- chromosomal fragments
- chromosome anomalies
radiation induced chromosome breaks may be viewed microscopically during
metaphase and anaphase of cell division
the effects of radiation induced chromosome breaks is
the visible difference in the structure of the chromosome
chromosome fragments
2 or more fragments are produced after chromosomal breakage
each has a fractured extremity and broken ends appear sticky and can adhere to another sticky end
2 types of chromosome anomalies observed at metaphase
- chromosome aberrations
2. chromatid aberrations
- chromosome aberrations
lesions that result when irradiation occurs early in interphase before DNA synthesis takes place
- chromatid aberrations
lesions that result when irradiation of an individual chromatid occurs later in interphase after DNA synthesis has taken place
4 consequences to the cell from structural changes in biologic tissue
- restitution
- deletion
- broken end rearrangement
- broken end rearrangement without visible damage to the chromatids
- restitution
a process in which chromosome breaks rejoin in their original configuration with no visible damage
- deletion
part of the chromosome or chromatid is lost at the next cell division creating an aberation known as an acentric fragment
- broken end rearrangement
where a grossly misshapen chromosome may be produced
- broken end rearrangement without visible damage to teh chromatids
where the chromatids genetic material has been rearranged even though the chromatid appears normal
target theory
a concept that the cell dies if inactivation of the master or key molecule occurs as a result of exposure to ionizing radiation
damage to cell’s nucleus can result in various types of ways (7 types)
- instant death
- reproductive death
- apoptosis or programmed cell death
- mitotic or genetic death
- mitotic delay
- interference with function
- chromosome breakage
instant death can occur when
the cells are irradiated with a high 1000 gray dose of xrays or gamma rays over a period of a few secs or mins
well above diagnostic range
instant death affects
vital functions of cytoplasmic organelles , the cell membrane, the nucleus and DNA
reproductive death
permanent loss of cells ability to reproduce because of exposure to doses of 1-10 gray
cell will function normally just won’t reproduce
apoptosis
cell that dies from radiation exposure before it attempts division
t or f
radiosensitivity of the cell governs the dose required to induce apoptosis
true
mitotic or genetic death
ionizing radiation affect cell division by retarding or by permanently inhibiting the mitotic process
can happen at small doses
mitotic delay
failure of a cell to divide on time
can occur when exposed to as little as 0.01 gray
after the delay the cell functions normal
interference of function
permanent or temporary interference of cell function independent of the cell’s ability to divide
chromosomal breakage
breaking of one or both sugar phosphate chains of DNA
cell survival curves
method of displaying the radiation sensitivity of a particular type of cell
vertical axis on cell survival curve
surviving fraction
horizontal axis on cell survival curve
radiation dose
immature cells
nonspecialized
more radiosensitive
undergo rapid cell division
mature cells
specialized
more radioresistant
divide at a slower rate or don’t divide at all
t or f LET affects cell radiosensitivity
true
hyperbaric oxygen
sometimes used in conjunction with radiation to treat certain types of cancers
law of bergonie and tribondeau formed when? and why?
1906
theorized and observed that radiosensitivity was a function of the metabolic state of the tissue being irradiated
law of bergonie and tribondeau states
the radiosensitivity of cells is directly proportional to their reproductive activity and inversely proportional to their degree of differentiation
hematologic depression is caused by how much dose delivered within a few days
0.25 Gyt
time necessary for bone marrow cells to recover depends on amount of radiation received
below 1 Gy =
repopulation occurs within weeks of irradiation
time necessary for bone marrow cells to recover depends on amount of radiation received
1-10 Gy or more =
severely depletes the # of bone marrow cells and require a longer recovery period
time necessary for bone marrow cells to recover depends on amount of radiation received
very high doses =
permanent decrease in number of stem cells
t or f
erythrocytes are among the most radiosensitive of human tissues
true
whole body doses in excess of 5 Gy
may die within 30-60 days
lethal dose of radiation for humans is specified as
LD 50/60
lethal dose of radiation for animals is specified as
LD 50/30
the lethal dose for humans in grays is
3-4 grays
what are the most radiosensitive blood cells in the human body
lymphocytes manufactured in bone marrow
a dose of what does what to neutrophils
a dose of 0.5 gray can cause a reduction in # of neutrophils present in blood
a dose of waht can do what to lymphocytes
a dose of .25 gray decreases the number of lymphocytes, but they can recover quickly
epithelial tissue is highly radiosensitive or radioinsensitive
radiosensitive
muscle tissue is highly radiosensitive or radioinsensitive
radioinsensitive
nerve tissue is highly radiosensitive or radioinsensitive
radioinsensitive
spermatogenia (germ cells) are highly radiosensitive or radioinsensitive
radiosensitive
mature = insensitive
immature = sensitive
radiation dose of 2 Gy to reproductive cells can cause
temporary sterility for as long as 12 months
radiation dose of 5 or 6 Gy to reproductive cells can cause
permanent sterility
radiation dose of 0.1 Gy to reproductive cells may
depress male sperm population
male reproductive cells exposed to dose of 0.1 Gy or more
may cause genetic mutations in future generations
radiation dose of 2 Gy to the ovaries may cause
temporary sterility
radiation dose of 5 Gy to the ovaries may cause
permanent sterility
small doses as low as 0.1 Gy to the ovaries may cause
menstrual irregularities
