Biological Effects of Radiation Flashcards
1
Q
What are two radiation effects on water?
A
- Primary Reactions (Direct Action)
- Secondary Reactions (Indirect Action)
2
Q
The ______ reactions are responsible for much of the biological damage caused by _____ LET radiations.
A
The primary reactions are responsible for much of the biological damage caused by high LET radiations.
3
Q
Define
What is a free radical?
A
- A highly chemically reactive form of an element due to the presence of an unpaired valence electron.
- It tries to combine chemically with other species so that its single unpaired electron can form a covalent bond with some other unpaired electron to complete its sub-shell.
4
Q
Is a free radical an ion?
A
No
- A free radical is electrically neutral.
- It has an equal number of protons in the nucleus to balance the negative electrons.
5
Q
What two free radicals are formed in irradiated water?
A
- Hydrogen radical (the hydrogen atom, not diatomic hydrogen)
- Hydroxyl radical (OH)
6
Q
What is the overall time span that primary reactions take place?
A
10-10 seconds
7
Q
What is the overall time span that secondary reactions take place?
A
10-5 seconds
8
Q
What are the three most probable secondary reaction equations?
A
9
Q
About ____ of the injuries produced by low LET radiation exposure to cellular DNA is traceable to the ______ radical.
A
About 2/3 of the injuries produced by low LET radiation exposure to cellular DNA is traceable to the hydroxyl radical.
10
Q
Pharmaceuticals useful for treating radiation accident victims fall into what two types?
A
- Treatement for external radiation exposure
- Treatment for internally deposited radioactive material
11
Q
What are the three different uses of drugs to treat external radiation exposure?
A
- Pre-irradiation protection to reduce the amount of damage at the time of exposure.
- After-irradiation pharmaceutical to repair damage at the molecular level.
- Pharmaceuticals used to “jump-start” the body into producing new stem cells.
12
Q
What is cystene used for?
A
- An organic compound that has been found to donate its hydrogens to neutralize hydroxyl free radicals.
- It has been found to raise the LD50/60 in humans by a factor of up to 1.7 times.
13
Q
How do you measure the usefullness of a protective agent?
A
- Dose Reduction Factor (DRF)
- DRF is the change to the normal lethal dose (LD50/30) for a test animal that can be produced.
14
Q
Define
LD50/30
A
The value of the dose delivered to a group of animals such that 50% of the exposed population will survive for 30 days without any medical treatment or intervention.
15
Q
Define
LD50/60
A
The value of the dose delivered to a group of humans such that 50% of the exposed population will survive for 60 days without medical treatment or intervention.
16
Q
What is the value for LD50/60?
A
410 rads +/- 150 rads
17
Q
Describe
Cell cycle
A
- G1 - Resting gap period
- S - Synthesis phase (15 hours while cell duplicatse its DNA)
- G2 - Resting gap period
- M - Mitosis (1 hour)
18
Q
Define
Biodosimetry
A
The methods in which changes caused by exposure to ionizing radiation are directly measured in a living system to determine the radiation dose received.
19
Q
Define
Checkpoint gene
A
- Gene p53 acts as a gatekeeper during the first resting phase G1 of the cell cycle.
- The cycle is put on hold by p53 if it detects DNA damage and only allowed to continue after repair has been completed.
- If p53 is mutated, cancer risk increases.
20
Q
Biodosimetry
What are the two different types of methods used in biodosimetry?
A
- Biological based techniques use detection of biological tissue damage (usualy at the cellular level).
- Physical measurements of changes induced by radiation in body tissues.
21
Q
Biodosimetry
What is an advantage and disadvantage of physical measurement techniques?
A
Advantage
- It can be performed at times well after the exposure incident.
Disadvantage
- The downside is that it will be unknown whether the dose measured was received at a particular time or is the result of cumulative exposures over a lifetime.
22
Q
Biodosimetry
What is an advantage and disadvantage of biological measurement techniques?
A
Advantage
- Biological measurements are more sensitive and can detect lower radiation doses than physical measurements.
Disadvantage
- Problems arise when it is realized that most of the biological damange is not completely radiation specific.
23
Q
Biodosimetry
The two most commonly analyzed tissues in physical biodosimetry are ____ and ____.
A
- Teeth
- Fingernails
24
Q
The Law of Bergonie and Tribondeau concluded that cells tend to be radiosensitive if they have what three properties?
A
- Cells have a high division rate.
- Cells have a long dividing future.
- Cells are of an unspecialized types.
25
_Define_
Relative Biological Effectiveness
The ratio of biological effectiveness of one type of ionizing radation relative to another, given the same amount of absorbed energy.
26
_Graph_
RBE vs. LET
27
_Graph_
Curves for various dose-response theories.
28
What are the four major types of cells in circulating blood?
1. Erythrocytes
2. Lymphocytes
3. Granulocytes
4. Platelets
29
What is the purpose of the human blood cell types?
* Erythrocytes - Oxygen transport to the cells
* Lymphocytes - Generate antibodies to fight infection
* Granulocytes - Fight infection by phagocytosis
* Platelets - Blood clotting agent and vessel integrity
30
_Acute Radiation Exposure_
In what exposure range does the GI tract become the leading organ of concern?
10 - 50 Sv
31
_Acute Radiation Exposure_
In what range does the Central Nervous System become the leading organ of concern?
Over 50 Sv
32
_Acute Radiation Exposure_
What is the "Therapeutic Range" for radiation exposure? What is the concern?
1 to 10 Sv
* Maintenance of minimum levels of circulating blood cells.
* Because blood cells originate from stem cells in the bone marrow, the effects seen in this range are often referred to as the "Bone Marrow Syndrome"
33
_Define_
Late Effects
* Effects which exhibit themselves a period of years after an acute exposure.
* The incidence is generally dependent on the radiation dose, dose rate, age at the time of irradiation, and state of health.
34
There are four main types of genetic mutations that occur in humans and animals
1. Dominant mutations ⇒ Caused by a single gene from one of the parents to the offspring.
2. Receissive mutations ⇒ Result only if the same altered gene is furnished by both parents.
3. Chromosomal rearrangements ⇒ Lead to mutations by mixing up the order of the genetic code.
4. Multifactorial mutation ⇒ The result of multiple genes being involved with the additional probability of influence from environmental factors (e.g., eating habits).
35
_Define_
Doubling Dose
The radiation dose which, if delivered to a large population, would produce an additional number of mutations equal to the number of spontaneous (natural) mutations.
36
What are examples of genetic mutations?
* Anemia
* Down syndrome
* Asthma
* Diabetes
37
What is the BEIR VII (2006) estimated doubling dose?
82 +/- 29 rads
38
What type of risk estimate is the doubling dose?
Relative risk of genetic injury (the risk is compared to the natural mutation rate).
39
_Define_
Somatic Effects
The results produced directly in the exposed individual.
40
What are thre categories of somatic effects?
1. Life shortening (from accelerated aging)
2. Leukemia
3. Other cancers
41
_Define_
Dose Rate Effectiveness Factor
* Factor by which radiation cancer risks observed (following large acute doses) can be reduced when the same amount of radiation is delivered at low dose rates or in a series of small dose fractions.
* Created as a method to recognize the existence of biological repair mechanisms.
* The DREF could only be used for accumulated doses below 20 rem and dose rates less than 5 rem year-1.
42
What is the value for DREF?
_NCRP 64 (1980)_
* Between 2 and 10 for low LET radiations like X- and gamma rays.
* It should only be used for accumulated doses below 20 rem and dose rates less than 5 rem year-1.
_ICRP_ ⇒ 2
_BEIR VII_ ⇒ 1.5
43
_Prenatal Radiation Exposure_
What can radiation doses delivered during pregancy produce?
* Spontaneous abortion
* Malformed organs
* Mental/growth retardation
* Teratogenic effects
44
_Prenatal Radiation Exposure_
When is prenatal death observed?
When radiation is received during the preimplantation phase (the first 2 weeks after conception).
45
_Prenatal Radiation Exposure_
Production of deformed organs and limbs in the fetus is observed when?
During the organogenesis phase (2 to 6 weeks after conception)
46
_Prenatal Radiation Exposure_
After 6 weeks post-conception, radiation exposure has what effect?
* Stunted growth and possible mental retardation
* The peak for mental retardation seems to be from 8 to 15 weeks after conception
47
BEIR V (1990) concluded that doses up to _____ Sv, cancer mortality follows a _____ relationship, except for leukemia which follows a _____ relationship.
BEIR V (1990) concluded that doses up to _4_ Sv, cancer mortality follows a _linear_ relationship, except for leukemia which follows a _linear-quadratic_ relationship.
Amount of effect seen = cD
Amount of effect seen = cD + kD2
48
_Describe_
Mitotic cell death
* Reproductive cell death / cellular inactivation.
* Most common death from radiation.
* Cells die because of damaged chromosomes while trying to divide.
49
_Describe_
Apoptosis
* Programmed cell death that occurs normally
* Greek for “falling off”
50
_List_
Types of radiation damage
* Nonlethal damage
* Sublethal damage
* Potentially lethal damage
* Lethal damage
51
_Decribe_
Nonlethal radiation damage
Slows down, but does not stop, cell proliferation
52
_Describe_
Lethal radiation damage
Damage is irreparable, irreversible, and leads irrevocably to cell death.
53
_Describe_
Sublethal radiation damage
Cells be either be repaired, or accumulate more dose to become lethal.
This is the basis for fractionation in radiation therapy.
54
_Describe_
Potentially lethal radiation damage
Cell death/survival can be modified by post exposure environmental conditions.
55
_List_
Factors affecting sensitivity to radiation
* Size of sensitive structure
* Repair capacity
* Genetic redundancy
* Genome organization
* Chemicals (radiosensitizers/radioprotectors)
* Age and gender
* Temperature
* Dose rate
56
_Define_
Oxygen Enhancement Ratio (OER)
* OER is the ratio of the radiation dose given under anoxic conditions to produce a certain affect relative to a radiation dose given under full oxygenated conditions to produce the same effect.
* Oxygen is the “most biological” factor that modifies the radiation response. Oxygen increases ⇒ Radiosensitivity increases
* Additional oxygen abundance creates additional free radicals which increase damage to target tissue.
57
_List_
Four R’s of Radiobiology
1. Repair
2. Reassortment/redistribution
3. Repopulation
4. Reoxygenation
58
_Describe_
Repair
(4 R's of Radiobiology)
* Prompt repair of sublethal damage
* Fractionating the dose allows time for cellular repair prior to receiving the full dose
59
_Describe_
Reassortment/redistribution
(4 R's of Radiobiology)
* Progression of cells through the cell cycle during the interval between radiation doses.
* Cell cycle moves from G2/M (growth and mitosis are radiosensitive) to S (synthesis is radioresistant)
60
_Describe_
Repopulation
(4 R's of Radiobiology)
* Increase of surviving fraction due to cell division
* Time interval between cell cycle is greater than cell cycle division time, which causes an increase in the number of cells surviving.
61
_Describe_
Reoxygenation
(4 R's of Radiobiology)
* Oxygen returns to hypoxic (oxygen depleted) cells increasing radiosensitivity.
* Applies to tumor/cancer cells and is another reason fractionation aids radiation therapy.
62
_List_
Required conditions for Acute Radiation Syndrome
* Radiation dose must be large (\> 0.7 Gy)
* Dose typically must be external
* Radiation must be penetrating (able to reach internal organs)
* Dose delivered over a short time (typically minutes)
63
_List_
Four stages of Acute Radiation Syndrome
* Prodromal syndrome (0 – 48 hours)
* Latent period (0 – 3 weeks)
* Manifest illness (0 – 8 weeks)
* Recovery or death (\> 6 – 8 weeks)
64
What are two direct effects of radiation on DNA?
Knocking-out tumor suppressor gene
* TP53 gene ⇒ Tumor suppressor gene that is lost or mutated in more than half of all human tumors.
* P53 protein ⇒ Produced by the gene controls arrest of cell cycle and pathway to apoptosis.
"Activating” oncogenes
* Oncogene ⇒ Gene that contributes to cancer formation when mutated or inappropriately expressed.
* “Activated” oncogenes ⇒ Allow bypass of apoptosis and enable proliferation of damaged/mutated cells.
65
_List_
Indirect effects of radiation
* Bystander effect ⇒ Effect extends to unirradiated cells, increasing the “target” cell population, or activing repair enzyme expression.
* Genomic instability
* Adaptive responses
* Threshold and/or hormesis
66
A woman is 10 weeks pregnant.
Give two reasons for and against taking a 2 rem X-ray on the woman’s abdomen.
_Support_
* Radiation induced malformations to the fetus are not likely after 10 weeks of pregnancy.
* Risks from cancer later in life are minimal for a dose of 2 rem in the abdominal area.
_Against_
* Other diagnostic tests might provide the desired diagnostic information.
* The desired diagnostic information will likely not aid in the medical treatment of the woman for her pregnancy.
67
List 3 possible effects of in-utero exposure at 10 weeks of pregnancy
1. Cancer in later life
2. Mental retardation
3. Congenital malformations
68
Why does the oxygen enhancement ratio decrease with increasing LET?
Oxygen modifies indirect effects, but does not modify direct effects
Indirect effects come from gammas and X-rays with low LET; therefore, as LET increases, the necessity for the presence of oxygen decreases.
69
What are the respiratory tract compartments?
* Upper respiratory tract
* Tracheal/bronchial tree
* Lymphatic
70
What are three pieces of information needed to determine the risk of injury to a fetus from a radiation exposure?
1. Age of fetus
2. Dose to fetus
3. Dose to risk conversion factors for the effects possible at that stage in gestation
71
Name three general types of biological effects of ionizing radiation that are taken into consideration in the derivation of dose limits for radiation workers
* Stochastic ⇒ Somatic effects (e.g., cancer)
* Non-stochastic ⇒ Deterministic effects (e.g., erythema)
* Genetic ⇒ Hereditary effects in the progeny of the exposed individual
72
_List_
Five deterministic effects resulting from exposure to acute, high dose rate ionizing radiation.
1. Cataracts
2. Epilation
3. Skin erythema
4. Desquamation (skin comes off in flakes)
5. GI syndrome
73
List three reasons for the increase to the risk coefficient in ICRP 60.
* Revised dosimetry of Japanese bomb survivors (neutron dose now considered insignificant)
* Change from an additive to a multiplicative risk projection model.
* Observed increase in total cancers (other than leukemia) in the Japanese study is still rising (largely a result of the excess mortality of those exposed as children).
74
What are the ICRP 60 risk coefficients for workers and the general public?
Worker ⇒ 0.04 Sv-1
General public ⇒ 0.05 Sv-1
75
What is the difference between an additive and multiplicative risk projection model?
Additive ⇒ Postulates broadly that the excess mortality is independent of normal mortality.
Multiplicative ⇒ Postulates there is a simple proportion between the natural cancer mortality and excess due to radiation for the whole time after the minimum latency period.
76
List three factors that contribute to the uncertainty of a specific risk factor calculation.
* Age ⇒ How the risk varies as a function of time for persons exposed at various ages.
* Dose ⇒ How the risk increases with dose.
* Normal incidence ⇒ Statistical uncertainty associated with the relatively small number of radiation induced cases observed in a population in a given category compared to normal incidence.
77
What will be the most likely effect from a 30 rem dose equivalent delivered to a fetus at 3 days, 3 weeks, and 3 months after conception?
3 days ⇒ Death
3 weeks ⇒ Teratogenic effects
3 months ⇒ Cancer
78
_Define_
Genetic doubling dose
The dose of radiation that produces twice the frequency of genetic mutations as would have been observed without radiation.
79
What is the range of the genetic doubling dose value?
What two studies were used to determine the genetic doubling dose?
50 – 250 rad
Megamouse and Fruit Fly experiments
