UNIT 2: Molecular & Cellular Radiation Biology Flashcards
1
Q
LET(Linear Energy Transfer)
A
amount of energy transferred on average by incident radiation to an object per unit length of track, or passage, through the object and is expressed in units of kiloelectron volts per micrometer.
2
Q
Free radicals
A
Solitary atoms, or most often a combination of altered atoms, that are very chemically reactive because of the presence of unpaired electrons
3
Q
RBE (Relative Biological Effectiveness)
A
describes the comparative capabilities of radiation with differing LETs to produce a particular biologic reaction.
4
Q
Anoxic
A
without oxygen
5
Q
Hypoxic
A
low oxygen
6
Q
OER (Oxygen Enhancement Ratio)
A
the radiation dose required to cause a particular biologic response of cell or organisms in any oxygen-deprived environment to the radiation dose required to cause an identical response under normal oxygen conditions
7
Q
Radiolysis
A
the dissociation of molecules by ionizing radiation
8
Q
Point lesion
A
when one of the sugar–phosphate chain side rails, or strands, of the ladder-like molecular structure ruptures (single-strand break)
9
Q
Mutation
A
the loss or change of a base in the DNA chain
10
Q
Erythrocyte
A
red blood cell without a nucleus that transport oxygen and carbon dioxide to and from the tissues.
11
Q
LD 50/30
A
dose that produces death in 50% of the subjects within 30 days (lethal dose to animals)
12
Q
LD 50/60
A
dose that produces death in 50% of the subjects within 60 days (lethal dose to humans)
13
Q
Leukocyte
A
(white blood cells) protect the body from infection
14
Q
Thrombocyte
A
(platelet) cell fragment found in large numbers in blood and involved in clotting
15
Q
What areas of study are included in Radiation Biology? (3)
A
• The sequence of events occurring after the absorption of energy from ionizing radiation
• The action of the living system to compensate for the consequences of this energy assimilation
• Injury to the living system that may occur from irradiation
16
Q
As LET increases, the chance of a significant biologic response in the radio-sensitive DNA
A
Increases
17
Q
By which means does Low LET cause damage to biologic tissue?
A
- X-rays
- Gamma Rays (short wavelength, high energy waves emitted by the nuclei of radioactive substances)
18
Q
Low LET is more likely to cause damage to biologic material through direct or indirect action?
A
Indirect
19
Q
Compare and contrast how Low LET and High LET cause damage to biologic material.
-Identify the one that is more damaging to biologic tissue.
A
-Potential risk of damage to DNA from high LET. Low can cause damage as well but not as much damage.
-High LET can cause more damage to biologic matter than low LET.
20
Q
High LET radiation penetrates more or less than Low LET radiation
A
Less
21
Q
Low LET Radiation Examples
A
• Gamma Rays
• X-rays
• Electrons
22
Q
High LET Radiation Examples
A
• Alpha Particles
• Ions of heavy nuclei
• Charged particles released from interactions between neutrons and atoms.
• Low energy neutrons
23
Q
Equation for RBE
A
Dose in Gy from 250 kVp x-rays / Dose in Gy of test radiation
24
Q
What is the purpose of RBE?
A
Used to describe biologic effectiveness of radiation of different quantities.
25
Where is RBE applied?
If the biologic effectiveness of radiation is known for x-rays, it will be used as a reference to figure out what the biological damage of a different type of radiation it will take to get the same effect as x-rays
26
Is RBE a useful application in radiation protection for humans?
Not really used in the diagnostic world because we use low LET, so we don’t need to test high LET for anything
27
Equation for OER
Radiation dose required to cause biologic response without oxygen / Radiation dose required to cause biologic response with oxygen
28
How does the presence of oxygen impact biologic damage with Low LET radiation
OER of 3.0 when radiation dose is high, can be 2.0 when radiation doses are below 2 Gy
29
How does the presence of oxygen impact biologic damage with High LET radiation
The presence or absence of oxygen is of little or no consequence to their effects. OER of about 1.0
30
Biologic damage from radiation can be observed on the following levels:
1. Molecular
2. Cellular
3. Organic Systems
31
Ionizing radiation interactions are produced in either:
1. Direct action
2. Indirect action
32
Direct Action
Primary photon has directly hit a molecule. Occurs more often in high LET because it can produce a lot of interactions.
33
Indirect Action
Multistep interaction, focuses on primary photons that interact with water molecules. Chances of primary photon hitting DNA is low because our bodies are made up of 80% water and only 1% DNA. Because we have more water than DNA, almost all biological damage comes from low LET.
34
During direct action, how does the absorption of energy through PE and Compton interactions cause damage to the macromolecules?
The ionization, or even the excitation, of the atoms of the biologic macromolecules can result in breakage of the macromolecules’ intricate chemical bonds, causing them to become abnormal structures.
35
What may result if the macromolecules are damaged during these events?
Essential biochemical processes that depend on the facilitating action of the enzymes may not occur in the cell when needed. A negative biologic sequence occurs.
36
RADIOLYSIS OF WATER is
Radiolysis 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.
37
Radiolysis of water events
1. Ionization of Water Molecules
2. Production of Free Radicals
3. Chemical Reactions & Biologic Damage
4. Cell Damaging Substances
5. Organic Free Radicals
38
Radiolysis of water: Ionization of Water Molecules
Separation into other molecular components. Interaction creates **positive water molecule and an electron**
39
Radiolysis of water: Production of Free Radicals
-Electron goes back to a positive water molecule (no cell damage) or electron can combine with neutral water molecule and create a **negative water molecule.**
-Negative and positive water molecules become unstable and break apart which creates **an ion pair and 2 free radicals.**
**Positive water molecule-** end up with positive hydrogen ion and a hydroxyl radical
**Negative water molecule-** end up with hydroxyl ion and hydrogen radical
40
Radiolysis of water: Chemical Reactions & Biologic Damage
Point lesions can occur. Free radicals can travel through the cell and can destructively interact with other molecules.
41
Radiolysis of water: Cell Damaging Substances
The hydroperoxyl radical and hydrogen peroxide are believed to be among the primary substances that produce biologic damage
42
Radiolysis of water: Organic Free Radicals
Radicals RO2* and HO2* are formed. These radicals can react with other organic molecules to cause biologic damage. Thus, a small-scale chain reaction of destructive events results when radiation deposits energy within tissue in the presence of oxygen.
43
How does the presence/absence of oxygen impact the production of organic free radicals?
Without oxygen or a force to attract an electron, these radicals usually react with each other to reform the original organic molecule (RH). When oxygen is present, however, R* and H* may react with oxygen molecules (O2) to form the radicals RO2* and HO2*
44
Specifically, what causes the immediate damage in an indirect action?
The by-products of the radiation, the **free radicals**, are the direct cause of this damage
45
How does the ratio between DNA & water in the body affect the likelihood of an indirect action event with low LET radiation?
The by-products of the radiation, the free radicals, are the direct cause of this damage. Because the human body is 80% water and less than 1% DNA, essentially all effects of low-LET irradiation in living cells result from indirect action.
46
What is the end result of radiolysis of water and how does this relate to indirect action of biologic damage?
The end result is the creation of free radicals which is the direct cause of biological damage in indirect action.
47
DNA with a Single Strand Break
(Point lesion) occurs with low LET radiation, unlikely to hit DNA but can still cause damage and result in gene abnormality. Repair enzymes can fix the damage to avoid consequences.
48
DNA with a Double Strand Break
Not easily repaired and can threaten the life of the cell. Occurs in high LET. Occurs in the same rung of DNA, genetic info can get lost in daughter cells and mutation can cause loss or change of a nitrogenous base in the DNA. The DNA gets “recoded”, and the wrong info can be passed down to the daughter cell. Can cause acute consequences.
49
Chromosome after a Double Strand Break in Same Rung of DNA molecule
The result will be the same as if both side rails of the ladder were severed at the same step, namely the DNA ladder would be chopped into two pieces. This situation will result in the associated chromosome to be broken. Thus, some types of chromosomal damage that are caused explicitly by high-LET radiation are related to double-strand breaks of DNA.
50
Chromosomal Fragments
Fragment can rejoin to their original configuration, or it can fail to rejoin and create an aberration. It can join other broken fragments to create new chromosomes.
51
How might a mutation occur as the result of radiation and what implications might this lead to?
**The loss or change of a base in the DNA chain represents a mutation.** Interactions of ionizing radiation with DNA molecules may cause the loss of or change in a nitrogenous base on the DNA chain. Damage may not be reversible and may generate acute consequences for the cell, but, more importantly, if the cell remains viable, incorrect genetic information will be transferred to one of the two daughter cells when the cell divides.
52
What are “sticky” ends?
After irradiation, some molecules can fragment or change into small, spur-like molecules that become very interactive (“sticky”) when exposed to radiation. Such sticky molecules can facilitate cross-linking by attaching or connecting to other macromolecules or other segments of the same macromolecule chain.
53
What are the 3 “sticky” ends outcomes?
1. Cross-links can happen between two places on the same DNA strand. This joining is an **intrastrand** cross-link.
2. Cross-linking may also take place between complementary DNA strands or between entirely different DNA molecules. These joining’s are **interstrand** cross-links.
3. DNA molecules also may become covalently linked to a protein molecule. These linkages are potentially fatal to the cell if they are not correctly repaired.
54
Chromosome aberrations
Chromosome aberrations result when irradiation **occurs early in interphase before DNA synthesis takes place.** The break caused by ionizing radiation is in a single strand of chromatin, which is the original chromosome. If repair is not complete before the start of DNA synthesis, this situation leads to a chromosome aberration in which both chromatids (the arms of the new chromosome) exhibit the break. **Each daughter cell generated will have inherited a damaged chromatid** because of a failure in the repair mechanism.
55
Chromatid aberrations
Solitary chromatid aberrations, conversely, result when irradiation of individual chromatids **occurs later in interphase, after DNA synthesis has taken place.** Then only one chromatid of the X-shaped pair may undergo a radiation-induced break. Therefore, **only one daughter cell is affected.**
56
Cell consequences: Restitution
The fragment rejoins the chromatid. No harm.
57
Cell consequences: Deletion
Chromosome or chromatid is missing, creates an aberration known as an acentric fragment. Cell mutation.
58
Cell consequences: Broken-End Rearrangement
Don’t look like typical chromosome. Cell mutation.
59
Cell consequences: Broken-End Rearrangement without Visible Damage
Chromatids look normal but the genetic material has been rearranged. Cell mutation.
60
Target Theory
photons either hit or don’t hit the master molecule (DNA) of the cell
61
What characteristics make up a master molecule?
Ensures cell survival, unique in any given cell, no similar molecules in the cell are available to replace it
62
What may cause the master molecule to become inactivated?
What may occur as a result of inactivation?
-If a critical location on the master molecule is a target receiving multiple hits from ionizing radiation, the master molecule may be inactivated
-Healthy cell function will then cease, and the cell will die.
63
Identify the master molecule of the cell
DNA
64
Radiation interacts with specific macromolecules by chance or seeking them out?
By chance
65
Cellular effects of radiation: Instant Death
-Occurs when an enormous amount of dose causes instant death
-Result: Cell’s DNA macromolecule breaks up and cellular proteins coagulate
66
Cellular effects of radiation: Reproductive death
-Cells have been damaged to the point where they can’t procreate
-Result: Prevent the transmission of damage to future generations of cells
67
Cellular effects of radiation: Apoptosis
-Cell death without attempting division
-Result: The cell nucleus breaks up and then the cell itself breaks up, and its fragments are usually ingested by neighboring cells
68
Cellular effects of radiation: Mitotic Death
-When cells die after 1 or more divisions
69
Cellular effects of radiation: Mitotic delay
-When cells do not divide on time
-Result: Delay can lead to alteration of chemicals involved in mitosis, proteins required in cell division not being synthesized, and a change in the rate of DNA synthesis after irradiation
70
Cellular effects of radiation: Functional Interference
-Permanent or temporary, repair enzymes can help the cell recover from interference function and help the cell go back to normal function.
71
What is the cell survival curve and how is most likely to be applied?
Displays the sensitivity of a particular type of cell to radiation
72
Another name for immature cells is nonspecialized, do they divide rapidly or at a slower rate?
Rapidly
73
Another name for mature cells is specialized, do they divide rapidly or at a slower rate?
Slower rate
74
Radio-sensitive Cell examples
-Basal cells of the skin
-Blood cells such as lymphocytes and erythrocytes
-Intestinal crypt cells
-Reproductive (germ) cells
75
Radio-insensitive (Radioresistant) Cells examples
-Brain cells
-Muscle cells
-Nerve cells
76
How is the concept of OER applied to treat cancers during radiation therapy?
Helps with treatment in radiation therapy, more oxygen can be administered to an area to make cells more sensitive and hopefully kill the bad cells for better results.
77
State the Law of Bergonie & Tribondeau
Radiosensitivity of cells is directly proportional to the reproductive activity and inversely proportional to their degree of differentiation. Thus, the most pronounce radiation effects occurs in the cells with the least maturity and specialization. This was first only applied to germ cells (reproductive cells) but, in fact, it is true to all types of cells.
78
LD 50/30 is generally applied to _________ where, LD 50/60 is applied to __________
Animals; Humans
79
The lethal whole-body dose for humans (without medical intervention) is estimated to be
3.0 to 4.0 Gy
80
What medical interventions may be employed to prolong life with this amount of exposure?
The use of antibiotics or isolation from pathogens in the environment (e.g., placing the patient in a sterile environment, feeding only sterilized food) has been proven to mitigate these effects in animals and humans
81
What role do leukocytes play in the body?
Help fight infection
82
The most radio-sensitive blood cell in the body is
Leukocytes
83
What radiation dose may decrease the number of leukocytes?
A whole-body radiation dose as low as 0.25 Gy
84
How might a decrease in leukocytes impact a person?
The body is highly susceptible to antigens
85
How long might it take for leukocytes to recover from a whole body radiation dose of 0.25Gy or less? 0.5 to 1 Gy?
-0.25Gy or less: shortly after irradiation
-0.5 to 1 Gy: several months
86
What role do neutrophils play in the body?
White blood cells that can also help fight infection.
87
What radiation dose may decrease the number of neutrophils?
0.5 Gy
88
What role do thrombocytes play in the body?
Platelets that initiate blood clotting and prevent hemorrhage.
89
What radiation dose may decrease the number of thrombocytes?
Range of 1 to 10 Gy
90
What effect might a reduction in thrombocytes have on an individual?
Wound clotting will be highly compromised
91
Describe the impact of undergoing imaging procedures in the diagnostic range might affect a person’s blood cells
Ionizing radiation can affect white blood cells and stem cells (radio-sensitive), we must limit reshoots and protect the patient while minimizing occupational exposure as well.
92
Explain why radiation therapy patients may need to have bi-weekly blood counts as part of treatment plan
A therapeutic dose of ionizing radiation, especially doses delivered to locations that include blood-forming organs, decreases the blood count. Biweekly blood counts are done to determine whether all of their functioning blood constituent counts are adequate.
93
Discuss why use of an OSL is preferred over blood count monitoring for occupational radiation workers
Biologic damage has already occurred when an irregularity is seen in the blood count. In addition, a blood count is a relatively insensitive test that is unable to indicate doses of less than 10 cGyt accurately.
94
What role do epithelial cells/ tissue play in the body?
Lines and covers body tissue
95
Epithelial cells are classified as radio-sensitive or radio-insensitive?
Radio-sensitive
96
Muscle cells are classified as radio-sensitive or radio-insensitive
Radio-insensitive
97
Describe the effects ionizing radiation can have on nerve cells?
Nerve tissues do not divide and are radio-insensitive
98
What dose of whole-body radiation may lead to death within a few hours or days as a result of severe damage to the CNS?
50 Gy
99
Nerve cells in the fetus are more or less sensitive than the adult nerve cells?
More
100
Identify CNS anomalies that may occur as a result of radiation in utero
Microcephaly (small head circumference), and intellectual disability
101
Which gestational time period is the CNS most sensitive stage?
Between 8-15 weeks
102
How does the CNS sensitivity compare between gestational weeks 8-15 and 15-25?
This time covers the end of neuron organogenesis (a period of development and change of the nerve cells) into the beginning of the fetal period. After this a lower level of elevated risk remains until week 25, at which time the risk is not found to be significantly different from that of young adults.
103
During the most sensitive period, what dose of radiation may lead to a drop in intellectual disability?
1.1 Sv (10 rem) fetal EqD is associated with as much as a 4% chance of intellectual disability.
104
If a patient is 12 weeks pregnant and her physician orders a lumbar myelogram, how might this impact the fetus? Why? What considerations should be taken into account and/ or discussed among the medical professionals?
The fetal EqD associated with abdominal fluoroscopy is generally about 0.05 Sv (5 rem). There could be a chance of intellectual disability. For such a situation a genetic study may be recommended afterwards.
105
What is the radio-sensitivity difference between mature and immature spermatogonia?
The male testes contain both mature and immature spermatogonia. Because the developed spermatogonia are specialized(mature) and do not divide, they are relatively insensitive to low-LET ionizing radiation. The “young” spermatogonia, however, are unspecialized(immature) and divide rapidly, and therefore these germ cells are very radiosensitive.
106
How can radiation dose affect sperm cells and female reproductive cells?
Dose:
2 Gy- temporary sterilization
5 to 6 Gy- permanent sterilization
107
Generally, what impact does diagnostic imaging have on the reproductive cells of male radiographers and patients?
Male reproductive cells that have been exposed to a radiation dose of 0.1 Gyt or more may cause genetic mutations in future generations. To prevent mutations from being passed on to children, male patients receiving this level of testicular radiation dose should refrain from unprotected sexual relations for a few months after such an exposure. Radiographers working under normal occupational conditions would never receive a gonadal dose of this level.
108
Describe the potential consequences that may occur if an irradiated female germ cell becomes fertilized
Genetic damage can be passed on to the child, potentially resulting in congenital abnormalities
109
Discuss the stages of radio-sensitivity of female germ cells from In Utero to advanced age
Birth to puberty: Ovaries are less radiosensitive
Puberty to 30: Decrease continues
30 to menopause: Increase in sensitivity
110
T/F: Adult nerves are radio-insensitive
True
