Ouhsc Radiobiology Test 2

Front 1

Every day mammalian cells incur over ____________ damaging events

Back 1

100,000

Front 2

What kind of damaging events happen in mammalian cells?

Back 2

Replication errors, base decay, attack by reactive oxygen species, or ionizing radiation

Front 3

What are repair pathways dependent on?

Back 3

The cell cycle (have to occur in specific sequences for them to act appropriately)

Front 4

What are enzymes relied upon to do?

Back 4

- remove unwanted or damaged components
- insert correct base(s) or sequence
- reunite the phosphate backbone of the helix

Front 5

Base Excision

Back 5

- repairs individual bases
- proofreading polymerase identifies mutation, endonuclease removes it, use opposite strand as template, DNA polymerase inserts correct base, DNA ligase ties everything back together

Front 6

Nucleotide Excision

Back 6

Removes dimers

Front 7

Single Strand Repair

Back 7

- if no bases are missing, simple ligation of helix is made
- w/ missing bases, DNA polymerase replaces them & DNA ligase ties everything back together

Front 8

Double Strand Repair - Homologous Recombination

Back 8

- intact sister chromatid acts as template in repair
- only time a sister chromatid is usable: after S phase, all the way through mitosis (anaphase is stopping point where fix can get done)
- less mutations

Front 9

Double Strand Repair - Nonhomologous End Joining

Back 9

- no guarantee that what we're repairing is what should've been there int he first place, no guarantee that it fixed what was lost
- can get complete deletions, translocations, or sequences than can be lost

Front 10

Crosslink DNA Repair

Back 10

DNA strand break linked to another molecule (protein)
- lethal if not repaired

Front 11

Mismatch DNA Repair

Back 11

- Replication errors
- Single Base --> hopefully proofreading polymerase fixes it
- Small Sequence Insertions --> sometimes an entire wrong sequence is put in, becomes a question of which side is correct

Front 12

Operational Classifications of DNA Damage - Lethal Damage

Back 12

Irreparable; cell dies

Front 13

Operational Classifications of DNA Damage - Potentially Lethal Damage (PLD)

Back 13

- damage that usually produces cell death if no repair occurs
- through repair cell has opportunity to survive
- repair is highly dependent on environmental conditions

Front 14

Operational Classifications of DNA Damage - Sublethal Damage (SLD)

Back 14

- under normal conditions repair is made (w/ ideal environment conditions)
- dependent on cell cycle phase & cell cycle synchrony

Front 15

PLD Repair

Back 15

- if a cell goes to 1st checkpoint marker in G1 & doesn't have proper condition to go into S phase, that delay will allow more time to repair (suboptimal conditions)
- radiation therapy implications
- cell survival increase

Front 16

SLD Repair

Back 16

- repair that occurs between fractionated doses
- less time between doses = lower survival fraction (more than 2 hours = end of window for repair)
- 3 Intervals: Repair, Reassortment, Repopulation

Front 17

SLD Repair - Repair

Back 17

Occurs promptly

Front 18

SLD Repair - Reassortment

Back 18

- progression through cell cycle
- results in cell synchrony through multiple irradiation events
- if it's timed appropriately, can kill off more cells (ex. tumors)

Front 19

SLD Repair - Repopulation

Back 19

Surviving fraction divides & grows

Front 20

SLD repair mechanism is dependent upon...

Back 20

Ability to repair DSB's

- multiple DSBs are bad
- purpose is to reduce formation of lethal lesions

Front 21

Repair vs. Radiation Quality

Back 21

- dependent on amount of SLD produced
- much less recovery potential for neutrons than x-rays b/c of the difference of mass (neutrons are high LET)
- in high LET there's more multiple DSBs, deletions, complete breakage of chromosomes

Front 22

Dose-Rate Effect

Back 22

- potential for cell survivability when we take given doses & spread them over time
- as dose rate is lowered & exposure time is increased, the effect of radiation is decreased
- as dose rate is decreased, curve flattens out b/c more cells start surviving

Front 23

Acute Administration

Back 23

A single high dose rate over a short period of time; creates more damage than can be repaired

Front 24

Inverse Dose-Rate Effect

Back 24

- decreased dose-rate causes increase in cell killing
- block is implemented at G2 (radiosensitive), survivability decreases
- any other dose outside the range of 1.54-0.37 Gy/hr will produce expected results

Front 25

Brachytherapy

Back 25

- implanted low dose rate radioactive sources placed close to tumors

Front 26

Intracavity Brachytherapy

Back 26

- radioactive material actively placed within a cavity in body that will help retain material so it will interact w/ tumor

Front 27

Interstitial Brachytherapy

Back 27

- encapsulated implants into or around tumor ("wires" or "seeds")
- continuous dose of radiation over time
- temporary or permanent

Front 28

Radiolabeled Immuoglobin Therapy

Back 28

- monoclonal antibodies: labeled antibody delivers radioisotope to tumor cell
- diagnostic, therapeutic

Front 29

Exposure to oxygen at the time of irradiation __________ (increases/decreases) the damaging effect

Back 29

Increases

Front 30

Oxygen Enhancement Ratio (OER)

Back 30

- ratio of doses administered under hypoxia to aerated conditions needed to produce the same biological effect
- effects were identified in 1940s by Gray

Front 31

The OER is dependent on....

Back 31

LET

Low LET produce HIGHER opportunity for OER
High LET produces greater damage

Front 32

Indirect Action of Oxygen Effect

Back 32

- production of ion pairs along charged particle tracks produce free radicals

Front 33

Free Radicals

Back 33

- break chemical bonds, make chemical changes
- in presence of oxygen, these react w/ DNA

Front 34

DNA radical can be quickly restored to normal through...

Back 34

Reaction w/ SH group

Front 35

Formation of RO2 makes damage...

Back 35

Semi-permanent (repairable only through DNA repair mechanisms)

Front 36

Hypoxic conditions _________ (enhance/reduce) RO2 production

Back 36

Reduce; less oxygen present for free radicals to combine with

Front 37

What determines hypoxia?

Back 37

Diffusion of oxygen through tissues

Front 38

Cells that are further away from oxygen source are ___________ (more likely/less likely) to be chronically hypoxic

Back 38

More likely

Front 39

Acute Hypoxia

Back 39

- occurs when blood flow is interrupted in a small blood vessel

Front 40

Chronic Hypoxia

Back 40

- causes cells to not repopulate or metabolize in the same manner

Front 41

How do tumors avoid hypoxia?

Back 41

- create their own blood supply
- structural integrity of blood vessels isn't normal (not strong enough to hold vessel open all the time)

Front 42

Reoxygenation

Back 42

- loss of cell numbers in localized areas can lead to this
- cell killing through radiation exposure treatment reduces cell numbers to increase oxygen diffusion in tissue (aerated cells die, hypoxic cells live)
- cells that survive become more radiosensitive

Front 43

How does hypoxia play a role in tumor malignancy?

Back 43

Through the opportunity for cells to recognize that they aren't getting oxygen they need

Front 44

Linear Energy Transfer (LET)

Back 44

- energy transferred through unit length of path traveled / expression of energy put down over a certain length of path
- units = keV/μm
- linear energy transfer (L) of charged particles in a medium is the quotient of dE/dl where dE = average energy locally imparted on the medium by a charged particle of specified energy in traversing a distance of dl

Front 45

LET vs. Energy

Back 45

LET is lower between 10 MeV protons & 150 MeV protons b/c as energy increases, the potential for this proton to transmit through tissues is decreased

Going to get to a point where the energy will have less of an effect on the amount of damage done b/c they transmit all the way through

Front 46

Relative Biological Effectiveness (RBE)

Back 46

- comparison of biological effect of different radiation types
- uses the effect of 250 keV x-rays as the standard

Front 47

National Bureau of Standards of RBE

Back 47

The RBE of some test radiation (r) compared with x-rays is defined by the ratio

D250/Dr

where D(sub)250 & Dr are, respectively, the doses of x-rays & the test radiation required for equal biological effect

Front 48

Factors that Determine RBE

Back 48

Radiation Quality
Dose (cell survival curve)
Number of dose fractions
Dose Rate
Biological system or endpoint

Front 49

Neutron curve will be __________ (steeper/less steep) than an electron curve

Back 49

Steeper; less shoulder on neutron curve (energy of neutrons much higher than electrons)

Front 50

RBE _______________ (increases/decreases) with fractionation of dose

Back 50

Increases

Low LET x-rays allow for repair between doses; increases total dose required to get to that point

Front 51

If mean lethal dose (LD50) for 250 keV x-rays is 8 Gy for an immortalized cell line & for neutrons is 4 Gy, RBE = ?

Back 51

2 (8/4)

Front 52

RBE as a Function of LET

Back 52

As LET increases beyond 10 keV/μm, RBE increases rapidly until 100 keV/μm then decreases rapidly

Front 53

What does the point at 100 keV/μm at which the ionization events are separated coincide with?

Back 53

The diameter of the DNA double helix

Front 54

Radiation Weighting Factor (WR)

Back 54

- quality factor of radiation
- used to calculate equivalent dose - convert rad to rem, Gy to Sy

Front 55

What does the radiation weighting factor help identify?

Back 55

Amount of dose being imparted to tissues based on the LET of the radiation in question

Front 56

Acute Radiation Syndrome

Back 56

- effect of high radiation exposure received in a single dose
- shortens life span depending on the dose & chance for recovery (5% for each 100 rads)
- expectation is a shortening of lifespan dose

Front 57

Median Lethal Dose (LD50/60)

Back 57

- specifies the lethal effect of radiation
- dose will cause 50% of the population to die within 60 days

Front 58

Immediately lethal doses cause death prior to how long?

Back 58

60 days

Front 59

LD50/60 is influenced by...

Back 59

Health, presence of bacteria, age, sex, environment

Front 60

3 Pathologic Processes caused by Radiation

Back 60

1) Necrosis/cell death
2) Hemorrhage
3) Infection

Front 61

Necrosis

Back 61

- occurs in most radiosensitive cells/tissues (lymph nodes, bone marrow, gonads, GI epithelium, skin)

Front 62

Hemorrhage

Back 62

- occurs mainly due to suppression of platelet formation
- damage to capillary walls is also evident which allows bleeding into other tissues
ex. skin (petechia), GI tract, respiratory system

Front 63

Infection

Back 63

- lack of body defense system
- occurs due to: loss of lymphocytes, immune system suppression, cell death, hemorrhage, anemia

Front 64

What are the 4 whole body syndrome stages?

Back 64

Prodromal Stage, Latent Stage, Manifest Sage, Recovery or Death Stage

Front 65

Prodromal Stage

Back 65

- happens right after dose is taken away
- Symptoms: malaise, nausea/vomiting (higher doses), fright

Front 66

Latent Stage

Back 66

- body seems to recover from exposure, won't exhibit any symptoms
- may last hours to days to weeks

Front 67

Manifest Stage

Back 67

- S&S of syndrome will be manifested
- progression of symptoms will occur
- at higher levels the symptoms of more than 1 syndrome may be apparent

Front 68

Recovery or Death Stage

Back 68

- dependent on 2 things: total exposure (REM) & treatment availability

Front 69

Subclinical Syndrome

Back 69

- occurs in ranges of 50-200ad (0.5-2 Gy)
- only PRODROMAL stage occurs
- less than 25 rads = no effect
- 20-100 Rad effects will occur in production of leukocytes

Front 70

Hematopoietic Syndrome

Back 70

- exposure ranges 250-500 Rad (2-5 Gy)
- death 2-3 weeks or up to 2 months

Front 71

Hematopoietic Syndrome - Prodromal Stage

Back 71

- can last 2 hours to 2 days
- nausea

Front 72

Hematopoietic Syndrome - Latent Stage

Back 72

- bone marrow & lymph nodes depleted of cells
- anemia occurs b/c of loss of RBC precursors

Front 73

Hematopoietic Syndrome - Manifest Stage

Back 73

- sore throat, fever, malaise, diarrhea
- LD50/60 is at 400 Rad exposure level
- have opportunity w/ good health care to overcome

Front 74

GI Syndrome

Back 74

- whole body exposures from 600-1000 R
- average survival = 6 days

Front 75

GI Syndrome - Prodromal Stage

Back 75

- occurs within hours
- watery diarrhea

Front 76

GI Syndrome - Latent Stage

Back 76

- may or may not occur depending on exposure dose (higher dose = less likely to occur)

Front 77

GI Syndrome - Manifest Stage

Back 77

- may come directly here from prodromal
- S/S: nausea, vomiting, prostration & elevated body temp
- epithelium of bowel lining flakes off & is removed
- death within 2 weeks w/ no treatment

Front 78

CNS Syndrome

Back 78

- very high exposures, 1000+ R
- onset of nausea & vomiting within minutes
- convulsions, brain edema happen due to cerebellum cell damage
- death within a few days

Front 79

Delayed Radiation Effects - Deterministic Effects

Back 79

- threshold is seen
- increased dose increases severity of effect

Front 80

Delayed Radiation Effects - Stochastic Effects

Back 80

- non-threshold
- increased dose increases probability of effect
- can appear to occur randomly within a population

Front 81

Sigmoid Dose-Response Curve

Back 81

- applies to most patients having radiation therapy
- characterized by S-shaped curve
- starts out w/ no effect until a certain dose is reached, then trends upward; will peak & effect will decline (even as dose is increased)

Front 82

Why does the effect decline as dose is increased on the Sigmoid Dose-Response Curve?

Back 82

Because at a certain point, we'll get to a quantity of dose where patients start dying

Front 83

Characteristics of Sigmoid Dose Response Curve

Back 83

Has dose-rate effect, has threshold, has deterministic effect

Front 84

Dose-Response Carcinogenesis

Back 84

- proposed by Gray who said that radiation-induced malignancy produces a bell shaped curve

Front 85

Linear Dose-Response Curve

Back 85

- ALL DOSES HAVE AN EFFECT
- most accepted version of application of radiation w/ expected effects
-

Front 86

What is the linear dose-response curve used to estimate?

Back 86

Upper limit effects, genetic effects, leukemia, & radiation induced cancers

Front 87

Damage itself may not be seen, but there is an expectation of...

Back 87

Damage occurring

Front 88

Characteristics of Linear Dose-Response Curves

Back 88

- no threshold (see effect as soon as dose applied)
- response is proportional to dose
- no dose-rate effects
- stochastic effects

Front 89

Linear-Quadratic Dose-Response Curve

Back 89

- sharp contrast between effects of doses at high vs. low level
- high level doses have a quadratic (squared) response
- low level doses have a linear relationship

Front 90

Characteristics of Linear-Quadratic Dose-Response Curves

Back 90

- no threshold
- low exposures = linear, high exposures = quadratic
- stochastic effects

Front 91

Carcinogenesis

Back 91

- increased frequency in exposed population
- stochastic effect (not everyone in population will get cancer)
- long latent periods for solid tumors

Front 92

What sources of human data have been used for radiation effects?

Back 92

Occupational exposure, atomic bomb survivors, medical exposure, fallout accidents in Pacific testing grounds

Front 93

Typical study performed to determine Radiation Induced Cancer Incidence

Back 93

- control group = general population (expected incidence of cancer)
- experimental group = irradiated population (incidence of cancer)
- calculating the irradiated population risk factor & expressing it as a rate

Rate = # of cancer cases/# exposed people (yr/rem)

Front 94

Problems with studies performed to determine Radiation Induced Cancer Incidence

Back 94

- no 2 health statuses are alike in experimental group
- number of people in general population w/ cancer compared to the total number of people in population is small fraction

Front 95

What are the most common carcinogenic effects of radiation?

Back 95

Leukemia, Breast / Thyroid / Lung / Bone / Stomach Cancer

Front 96

Breast Cancer (Carcinogenic Effects of Radiation)

Back 96

- Life Span Study: Hiroshima Survivors
- Nova Scotia & Massachusetts Studies (induced pneumothorax & fluoro)
- Rochester Study (acute postpartum mastitis w/ fluoro)

Front 97

Skin Cancer (Carcinogenic Effects of Radiation)

Back 97

- occurred in physicians & dentists holding patients during x-ray exposures
- usually either basal cell or squamous cell carcinoma (basal cell 4x more likely)

Front 98

Bone Cancer (Carcinogenic Effects of Radiation)

Back 98

- found in radium watch dial painters; ingested radium, which deposited into bone
- children treated for tinea capitis (fungal infection of skin)

Front 99

Liver Cancer (Carcinogenic Effects of Radiation)

Back 99

- thorotrast: contrast agent that contained thorium used for liver radiography & angiography
- patients have shown increased incidence of cancer
- caused by alpha particles released as thorium decayed

Front 100

Lung Cancer (Carcinogenic Effects of Radiation)

Back 100

- uranium miners inhaled radon gas & radioactive dust; high incidence of cancer in bronchial epithelium (higher than atomic bomb survivors)
- 8x more likely to have cancer from job; 20x more if they also smoke

Front 101

Leukemia (Carcinogenic Effects of Radiation)

Back 101

- seen in Japanese atomic bomb survivors
- Ankylosing Spondylitis (used x-rays to treat, 12x higher rate of leukemia)

Front 102

Thyroid Cancer (Carcinogenic Effects of Radiation)

Back 102

- radiation therapy for thymus enlargement
- sometimes have 10 year latent period
- non-aggressive cancer

Front 103

Radiation Therapy Induced Carcinogenesis

Back 103

- secondary malignancies produced from exposure from treatment
- factors such as lifestyle & age have a higher chance of causing additional malignancies

Front 104

Who are at highest risk for radiation induced cancer?

Back 104

Nuclear industry workers, radiologists (used to be), children in utero

Front 105

Life Span Shortening

Back 105

- stochastic & non-specific shortened lifespan a result of other specific causes

Front 106

Theories on Life Span Shortening

Back 106

1) Radiation will cause normal aging at a faster rate
2) Radiation will cause an individual to be more sensitive to specific diseases
3) Life span shortening is due to point mutations of the genes & chromosomal rearrangements

Front 107

Radiation Hormesis

Back 107

- frequent low level radiation exposure produces a protective effect (school of thought)
- impact it has on cell/DNA repair mechanism

Front 108

Decreasing Incidence of Radiation Induced Cancer

Back 108

- increased knowledge of effects of radiation
- strict regulations
- radiation no longer utilized as treatment for everything