Chapter 7- Molecular and Cellular Radiation Biology Flashcards
Branch of biology concerned with the effects of ionizing radiation on living systems
Radiation Biology
what does Radiation Biology include of:
Sequence of events occurring after the absorption of energy from ionizing radiation
Action of the living system to make up for the consequences of this energy assimilation
Injury to the living system that may be produced
Damages living systems by ionizing the atoms comprising the molecular structure of these systems
IONIZING RADIATION
Biologic damage begins with the ionization produced by various types of radiation such as
Xrays
Gamma rays
Alpha particles
Beta particles
Protons
TRUE OR FALSE:
Ionized atoms will not bond properly in molecules
True
what varies among the different types of radiation
Charge, mass, and energy vary among the different types of radiation
**These attributes determine the extent to which different radiation modalities transfer energy into biologic tissue.
Three important concepts help us to understand the way ionizing radiation causes injury and how the effects may vary in biologic tissue.
Linear energy transfer
Relative biologic effectiveness
Oxygen enhancement ratio
The average energy deposited per unit length of track by ionizing radiation as it passes through and interacts with a medium along its path
Linear Energy Transfer (LET)
What does LET stand for
Linear Energy Transfer
what units is LET described in
Is described in units of keV/μm
Is a very important factor in assessing potential tissue and organ damage from exposure to ionizing radiation
LET
Radiation categories according to LET
Low-linear energy transfer radiation
High-linear energy transfer radiation
Examples of Low LET radiation
Gamma Rays and Xrays
Examples of high LET Radiation
-alpha particles
-ions of heavy nuclei
-charged particles released from interactions between neutrons and atoms
-low energy neutrons
Describes the relative capabilities of radiation with differing LETs to produce a particular biologic reaction
Relative Biologic Effectiveness (RBE)
What does RBE stand for
Relative Biologic Effectiveness
is the ratio of the dose of a reference radiation (conventionally 250-kVp x-rays) to the dose of radiation of the type in question that is necessary to produce the same biologic reaction in a given experiment. The reaction is produced by a dose of the test radiation delivered under the same conditions.
RBE of the type of radiation being used
The ratio of the radiation dose required to cause a particular biologic response of cells or organisms in any oxygen-deprived environment to the radiation dose required to cause an identical response under normal oxygenated conditions
Oxygen Enhancement Ratio (OER)
when the radiation dose is high, how much OER does xrays and gamma rays have
In general, x-rays and gamma rays have an OER of about 3.0 when radiation dose is high.
when the radiation dose is low, how much is the OER
ER may be less (approximately 2.0) when radiation doses are below 2 Gyt.
what is the OER ratio
radiation dose required to cause biologic responce without O2 over Radiation dose required to cause biologic response with O2
In living systems, biologic damage stemming from exposure to ionizing radiation may be observed on three levels
Molecular
Cellular
Organic systems
Any visible radiation-induced injuries of living systems at the cellular or organic level always begin with damage at what level
at the molecular level.
results in the formation of structurally changed molecules that may impair cellular functioning.
Molecular Damage
what is the relationship between LET and RBE
directly proportional
As LET increases, what happens to the biologic damage
LET increases, biologic damage increases
what happens to the energy as there is an increase in LET and increase in RBE
decrease in energy
what happens to energy when there is a decrease in LET and RBE
increase in energy
Is low LET less or more damaging than High LET
Low LET is less damaging because there is not as much deposited.
which term means most sensitive
least resistant
which term means least sensitive
most resistant
what is the RBE ration
Dose in Gy over the dose of test radiation
Somatic
yourself
Genetic
future generations
Three things that can happen in the molecular, cellular, or organic systems
-repair (no damage)
-mutated
-cell death
Because energy from ionizing radiation can alter a human cell’s constituent molecules, such exposure may disturb the cell’s chemical balance and ultimately the way it operates. The affected cell can then no longer perform its normal task.
If a sufficient quantity of somatic cells are affected, entire body processes may be disrupted.
If radiation damages the germ cells, the damage may be passed on to future generations in the form of genetic mutations.
Effects of Irradiation on Somatic and Genetic Cells
There are two classifications of ionizing radiation interaction on a cell.
Direct action (e.g., in DNA)
Indirect action (e.g., in H2O)
directly hitting DNA (more common with Alpha)
Direct
is high LET direct or indirect
direct
hitting something else not DNA
indirect
is low LET direct or indirect
indirect
is direct or indirect more likely to happen
Indirect —-Because the human body is 80% water and less than 1% DNA, essentially all effects of low-LET irradiation in a living cell result from indirect action.
what happens when free radicles comes in contact with DNA
there will be cell death
what does a indirect hit create
indirect hit creates free radicals, those free radicals cause more biological damage
What are the steps of Radiolysis of water
Ionization of water molecules
Production of free radicals
Production of undesirable chemical reactions and biologic damage
Production of cell-damaging substances
Organic free radical formation
only effecting the one side of rungs
single strand
-can be cell death (not commonly repaired)
-usually happens with alpha
Double strand break
Ionizing radiation interacts with DNA macromolecule, transfers energy, and ruptures one of the molecule’s chemical bonds possibly severing one of the sugar-phosphate chain side rails (called a point mutation)
Repair enzymes are often capable of reversing this damage
single strand break
what type of radiation does Double strand break happen with
Occur more commonly with densely ionizing (high-LET) radiation.
Further exposure of the affected DNA macromolecule to ionizing radiation can lead to additional breaks in the sugar-phosphate molecular chain(s).
Breaks may also be repaired but are not repaired as easily as single-strand breaks.
If repair does not take place, further separation may occur in the DNA chains, threatening the life of the cell.
Double strand break
what terms means between same dna strand
intrastrand cross link
what term means between two different strands
interstrand cross link
Result is a cleaved or broken chromosome with each new portion containing an unequal amount of genetic material
If damaged chromosome divides, each new daughter cell will receive an incorrect amount of genetic material culminating in the death or impaired functioning of the new daughter cell.
double strand break in same rung of dna
Interactions of ionizing radiation with DNA molecules may cause the loss of or change in a nitrogenous base in the DNA chain.
Mutation
Direct consequence of this damage is an alteration of the base sequence,
a mutation
consequences for the cell
If cell remains viable, incorrect genetic information will be transferred to one of the two daughter cells when the cell divides.
Mutation
Interactions of ionizing radiation with DNA molecules may cause the loss of or change in a nitrogenous base in the DNA chain.
Direct consequence of this damage is an alteration of the base sequence, a mutation.
May not be reversible and may cause acute consequences for the cell
If cell remains viable, incorrect genetic information will be transferred to one of the two daughter cells when the cell divides.
mutation
Chemical unions created between atoms by the single sharing of one or more pairs of electrons
Initiated by high-energy radiation
(happens because of alpha, beta)
Covalent CROSS LINKS
sharing of one or more pairs of electrons
Initiated by high-energy radiation
Following irradiation, some molecules can fragment or change into small, spurlike molecules that become very interactive (sticky) when they themselves are exposed to radiation, causing these molecules to attach to other macromolecules or to other segments of the same macromolecule chain.
Can occur in many different patterns.
Covalent cross links
is U seen in DNA or RNA
RNA
Large-scale structural changes in a chromosome produced by ionizing radiation may be as grave for the cell as are radiation-induced changes in DNA.
Effects of Ionizing Radiation on Chromosomes
Radiation-induced chromosome breaks in both somatic and reproductive cells
list the types:
-Chromosomal fragments
-Chromosome anomalies
-Chromosome aberrations
-Chromatid aberrations
-Structural changes in biologic tissue caused by ionizing radiation
Chromosomal fragments
producing 2 or more chromosomal fragments
-be fine
-aboration
-deformity
refers to the dissociation of molecules by ionizing radiation. Thus, when x-ray photons interact with water molecules contained within the human body, this can result in their separation into other molecular components.
radiolysis
After chromosome breakage, two or more chromosomal fragments are produced. Each of these fragments contains a fractured extremity. These broken ends are chemically very active and therefore have a strong tendency to adhere, or chemically combine, to another similar end
chromosomal fragments
The fractured fragments can:
- Rejoin in their original configuration
- Fail to rejoin and create an aberration (lesion or anomaly)
- Join to other broken fragments and thereby create new chromosomes that may not appear structurally altered compared with the chromosome before irradiation
Two types of chromosome anomalies have been observed at metaphase. They are:
- Chromosome aberrations and
- Chromatid aberrations
where does chromosome anomalies happen
metaphase
result when irradiation occurs early in interphase, before DNA synthesis takes place. In this situation, the break caused by ionizing radiation is in a single strand of chromatin, which is the original chromosome
chromosome aberrations
happens early interphase, break is visible in next mitosis phase
each daughter cell will have damage
chromosome aberrations
chromotid abberations
1 daughter cell is effected
Summary of structural changes caused by ionizing radiation.
- A single-strand break in one chromosome
- A break in one chromatid
- A single-strand break in separate chromosomes
- A strand break in separate chromatids
- More than one break in the same chromosome
- More than one break in the same chromatid
- Chromosome stickiness, or clumping together
the breaks rejoin in the original configuration with no visible damage.
Restitution
The process of deletion, in which part of a chromosome is lost at the next cell division, thus creating an acentric fragment.
Deletion
-form of mutation
-fully seperated off
-part of chromosome is lost at the next cell division , thus creating an acentric fragment
Deletion
a grossly misshapen chromosome may be produced. Ring chromatids, dicentric chromosomes, and anaphase bridges are examples of such distorted chromosomes and chromatids (Fig. 7.13). This results in a cell mutation.
Broken end ararrangment
whereby the chromatid’s genetic material has been rearranged, yet the chromatid appears normal. Translocations are examples of such rearrangements (Fig. 7.14). This results in a cell mutation
Broken-end rearrangement without visible damage to the chromatids
This concept of radiation damage to specific sensitive locations resulting from discrete and random events is known
target theory
molecule that maintains normal cell function is believed to be present in every cell.
a master or key molecule
what molecule is necessary for the survival of the cell
Master, or key, molecule is necessary for the survival of the cell.
what may be used to explain cell death and nonfatal cell abnormalities caused by exposure to radiation.
target theory
Damage to the cell’s nucleus reveals itself in one of the following ways.
Instant death
Reproductive death
Apoptosis, or programmed cell death (interphase death)
Mitotic, or genetic, death
Mitotic delay
Interference with function
three energy transfers
LET
RBE
OER
-high(alpha, heavy nuclei) and low (XR and gamma)
-average energy deposited per unit length of track
LET
comparative capabilities of radiation with differing LET’s to produce a particular biologic reaction
RBE
when tissue is in oxygenated state- more sensitive
OER
without oxygen
anoxic
low oxygen
hypoxic
what type of cells are 3x more resistant
cells that are anoxic
ratio for OER
radiation dose without oxygen over with oxygen
what does free radicals do to the biologic damage
biologic damage is increased
indirect can be repaired with or without oxygen
without oxygen
indirect can be lasting/fixed with or without oxygen
with oxygen
biologic damage occurs as a result of DNA - inactive/functionally disable (high LET)
direct action
most are these
interact with water (80-85%)
produce free radicals
indirect action
-one chemical bond
-side rail on strand
-point mutation - Low LET
-repair enzyme can repair
DNA single strand
what type of strand:
-high LET
-not usually repaired
Double strand
same DNA strand
intrastrand
two different ones
interstrand
DNA is directly or indirectly inactivated by exposure- radiation to the cell will cause death
-random event that causes radiation damage
target theory
radiosensitivity of a certain type of cell
cell survival curve
single most sensitive cell in body
lymphocyte
true or false
diagnostic xrays are considered low LET radiation
true
-defines the rate of energy deposited per unit track length through an absorber
-amount of radiation that is transferred to the body as the xray beam travels
-as LET increases the quality factor for a given form of radiation will increase
-is greatest for emissions of particulate matter, such as alpha particles, and lowest for X and gamma radiation
LET
-defines the ability or aerobic conditions to enhance the effectiveness of radiation
-increasing the oxygenation of a cell increases the cells sensitivity to radiation
-is a numeric description of the oxygen effect. OER for human tissues has a max of approx. 3.0
oxygen effect
-defines the ability to produce biologic damage
-increasing LET radiation will result in an increase in biologic damage
-diagnostic xrays are considered low LET radiation
RBE
-Radiation interaction with water ( ionization of water molecules
if positive no damage, restabilize
if negative will not stabilize)
-photon-water interaction results in ionization of water
-positive water molecule can split into a free radical - highly reactive and unstable substance
-free radicals can combine to form toxic substances such as hydrogen peroxide (OH2 + OH2= H2O2)
-radiation is indirectly the cause of biologic damage
-vast majority of radiation damage to the body is caused by the indirect action of radiation interacting with water due to the large amount of water contained in typical cell
Radiolysis
altering areas of chemical bond
point lesion
true or false
if radiation interacts with water it can form an ion pair
2/3 pairs is called by free radicals
true
true or false
metaphase is the most sensitive
true
true or false
cells vary in their radiosensitivity
true
is a classic method of displaying the sensitivity of a particular type of cell to radiation.
cell survival curve
how is the cell survival curve obtained
Curve is constructed from data obtained by a series of experiments.
Radiosenistive cells
BASAL CELLS OF SKIN
BLOOD CELLS SUCH AS LYMPHOCYTES AND ERYTHROCYTES
INTESTINAL CRYPT CELLS
REPRODUCTIVE (GERM) CELLS
Amount of radiation energy transferred to biologic tissue
Plays a major role in determining the amount of biologic response
As LET increases, the ability of the radiation to cause biologic effects also generally increases until it reaches a maximal value.
LET can influence cell radiosensitivity.
CELL RADIOSENSITIVITY
Oxygen enhances the effects of ionizing radiation on biologic tissue by increasing tissue radiosensitivity.
During diagnostic imaging procedures, fully oxygenated human tissues are exposed to x-radiation or gamma radiation.
In radiotherapy, when radiation is used to treat certain types of cancerous tumors, high-pressure (hyperbaric) oxygen has sometimes been used in conjunction with it to increase tumor radiosensitivity.
OXYGEN ENHANCEMENT
Observed the effects of ionizing radiation on testicular germ cells of rabbits they had exposed to x-rays
Law of Bergoiné and Tribondeau
Established that radiosensitivity was a function of the metabolic state of the cell receiving the exposure
Law of Bergoiné and Tribondeau
States that the radiosensitivity of cells is directly proportional to their reproductive activity and inversely proportional to their degree of differentiation
Law of Bergoiné and Tribondeau
Observed the effects of ionizing radiation on testicular germ cells of rabbits they had exposed to x-rays
Established that radiosensitivity was a function of the metabolic state of the cell receiving the exposure
States that the radiosensitivity of cells is directly proportional to their reproductive activity and inversely proportional to their degree of differentiation
Law of Bergoiné and Tribondeau
Law was originally applied only to germ cells; it is actually true for all types of cells in the human body.
The most pronounced radiation effects occur in cells having the least maturity and specialization or differentiation, the greatest reproductive activity, and the longest mitotic phases.
Law of Bergoiné and Tribondeau
true or false
The more mature and specialized in performing functions a cell is, the less sensitive it is to radiation.
true
Equal doses of ionizing radiation produce different degrees of damage in different kinds of human cells because of differences in cell radiosensitivity.
The more mature and specialized in performing functions a cell is, the less sensitive it is to radiation.
Effects of ionizing radiation on human cells
Effects of ionizing radiation on human cells (Cont.)
Blood cells
-Hematologic depression
-Depletion of immature blood cells
-Repopulation after a period of recovery
-Effects on stem cells of the hematopoietic system
-Whole-body doses in excess of 5 Gyt
-Effects of ionizing radiation on lymphocytes
- Effects of ionizing radiation on neutrophils
-greater than diagnostic studies
-1000 Gy over period of seconds
instant death
results from exposure of cells to doses or ionizing radiation in the range of 1-10 Gy
loses ability to procreate
reproductive death
programmed cell death
interphase death
dies without attempting to divide again
apopotosis
A non-mitotic, or non-division, form of cell death that occurs when cells die without attempting division during the interphase portion of the cell life cycle is
Apoptosis
occurs when a cell dies after one or more divisions. Even relatively small doses of radiation have a possibility of causing this type of cell death. The radiation dose required to produce mitotic death is less than the dose needed to produce apoptosis in slowly dividing cells or non-dividing cells.
mitotic death
the failure of the cell to start dividing on time. After this delay the cell may resume its normal mitotic function.
mitotic delay
reasons for mitotic delay
- Alteration of a chemical involved in mitosis
- Proteins required for cell division not being synthesized
- A change in the rate of DNA synthesis after irradiation
radioinsensitive cells
brain cells
muscle cells
nerve cells
immature, nonspecialized, rapid cells division- germ cells, lymphocytes
radiosensitive
more mature, specialized divide slower rate- nerve, muscle
radioinsensitive
oxygen present =free radicals
increased indirect damage
increased oxygen , increased radiosensitivity
oxygen enhancement
immature/nonspecialized -more sensitive
Law of Bergoiné and Tribondeau
.25 Gy whole body in a few days- exceeds dose for population
-blood tests not valid for dosimetry purpose
hemotologic depression
after recovery , bone marrow can repopulate if wasnt destroyed
-recovery depends on dose
-less than 1Gy=weeks
-1-10 Gy + greater than 10 =
can cause permanent decrease
repopulation
RBC -oxygen to tissues and organs
-among most radiation (mature vs immature)
-not usually cause of death - Increase repopulation
effects of stem cells
Permanent or temporary interference with cellular function independent of the cell’s ability to divide can also be brought about by exposure to ionizing radiation. If repair enzymes are able to repair the damage, the cell can recover and continue to function properly. Otherwise, the cell will be unable to reproduce or will die.
interference with function
Most blood cells are manufactured in the bone marrow. Radiation causes a decrease in the number of immature blood cells (stem or precursor) produced in the bone marrow and hence a reduction, ultimately, in the number of mature blood cells in the bloodstream. The higher the radiation dose received by the bone marrow, the higher will be the resulting cell depletion
depletion of immature blood cells
