RAB: ch.20 Radiation Biology

Question 1

Adverse biological effects from ionizing radiation were observed shortly after __________’s discovery of x-rays in year ____ and _________’s discovery of __________ in ____.

Answer 1

Wilhelm Conrad Roentgen, 1895

Becquerel, 1896

Question 2

The study of the action of ionizing radiation on healthy and diseased tissue is the scientific discipline known as _________?

Answer 2

radiation biology

Question 3

[Determinants of biologic effects of radiation]

What are the 3 radiation-related factors?

Answer 3

1. absorbed dose (quantity)
2. dose rate
3. type and energy (quality) of radiation

The radiosensitivity of a complex biologic system is determined by a num

Question 4

How do you classify the Biologic Effects of radiation exposure?

Answer 4

• Stochastic effect
• Deterministic effect

Question 5

One in which the probability of the effect occurring, (rather than its severity), increases with dose.

Answer 5

Stochastic effect

Radiation-induced cancer and hereditary effects are stochastic in nature. For example, the probability of radiation-induced leukemia is substantially greater after an exposure to 1 Gy than to 10 mGy, but there will be no difference in the severity of the disease if it occurs

Question 6

Regarded as the principal health risk from low-dose radiation, including exposures of patients and staff to radiation from diagnostic imaging procedures?

Answer 6

Stochastic effect

Question 7

T or F?
Stochastic effects are believed not to have a dose threshold, because damage to a few cells or even a single cell could theoretically result in production of the disease.

Answer 7

True

It is this basic, but unproven, assumption that risk increases with dose and there is no threshold dose below which the magnitude of the risk goes to zero, that is the basis of modern radiation protection programs, the goal of which is to keep exposures as low as reasonably achievable

Question 8

If a radiation exposure is very high, the predominant biologic effect is _____, which presents clinically as degenerative changes in the exposed tissue.

Answer 8

cell killing

Question 9

The severity of the injury, (rather than its probability of occurrence), increases with dose.

Answer 9

Deterministic effect

Question 10

T or F:
Deterministic effects (also referred to as tissue reactions) differ from stochastic effects in that they require much higher doses to produce a clinically observable effect and there is a threshold dose below which the effect does not occur or is subclinical.

Answer 10

True

Question 11

What are examples of deterministic effects that can result from large radiation exposures?

Answer 11

• Skin erythema
• fibrosis
• hematopoietic damage

Question 12

___ effects can be caused by severe radiation accidents and can be observed in healthy tissue that is unavoidably irradiated during radiation therapy.

Answer 12

Deterministic

Question 13

T or F:
In the context of diagnostic x-ray exposure, cell death does not mean the acute physical destruction of the cell by radiation but rather a radiation-induced loss of mitotic capacity (i.e., reproductive death) or premature activation of apoptotic pathways (i.e., programmed cell death). There is considerable evidence that damage to DNA is the primary cause of radiation-induced cell death.

Answer 13

True

Question 14

Spectrum of DNA Damage The deposition of energy (directly or indirectly) by ionizing radiation induces chemical changes in large molecules that may then undergo a variety of structural changes. These structural changes include ___?

Answer 14

1. hydrogen bond breakage
2. molecular degradation or breakage
3. intermolecular and intramolecular cross-linking.

Question 15

True or False:
Molecular breakages also may involve the sugar-phosphate polymers that comprise the backbones of the two helical DNA strands. They may occur as single-strand breaks (SSBs), double-strand breaks (DSBs) (in which both strands of the double helix break simultaneously at approximately the same nucleotide pair), base loss, base changes, or cross-links between DNA strands or between DNA and proteins.

Answer 15

True

Question 16

A type of molecular breakage where the sugar and phosphate can rejoin, provided there is no opportunity for the broken portion of strands to separate.

Answer 16

SSB (single-strand breaks)

Question 17

___ can occur if two SSBs are juxtaposed or when a single, densely ionizing particle (e.g., an alpha particle) produces a break in both strands. DNA DSBs are very genotoxic lesions that can result in chromosome aberrations.

Answer 17

Double strand breaks (DSB)

Question 18

Regardless of its severity or consequences, the loss or change of a base is considered a type of ____

Answer 18

mutation

Question 19

chromosome breaks produced by radiation do occur and can be observed microscopically during ___and ___, when chromosomes are condensed.

Answer 19

anaphase, metaphase

Question 20

In DNA repair, the cell may activate _ checkpoint (which arrests cell cycle progression), to allow for repair of damaged or incompletely replicated chromosomes.

Answer 20

G1/S checkpoint

Question 21

___ is a form of cell death that is characteristically different from cell necrosis in morphology and biochemistry, leading to the elimination of cells without releasing inflammatory substances into the surrounding area. Apoptosis results in cell shrinkage via nuclear condensation and extensive membrane blebbing ultimately resulting in the fragmentation of the cell into membrane bound apoptotic bodies composed of cytoplasm and tightly packed organelles that are eliminated by phagocytosis.

Answer 21

Apoptosis (programmed cell death)

Question 22

What are the types of DNA reparie mechanisms

Answer 22

• direct repair of a damaged nucleotide
• short and long patch base excision repair (SP BER, LP BER)
• nucleotide excision repair (NER)
• SSB and DSB repair
• cross-link repair

Question 23

Most DNA base damage and SSBs are repaired by the ___?

Answer 23

base excision repair pathway

Question 24

___ is the major pathway for the repair of bulky, helix-distorting lesions such as thymine dimers produced by exposure to ultraviolet radiation.

Answer 24

nucleotide excision repair (NER)

Question 25

True or False:
DNA repair occurs rapidly, and approximately 90% of SSB and base damage is repaired within an hour after the initial damage. Even with DSBs, DNA rejoining is virtually complete with 24 hours

Answer 25

True

Question 26

How do you classify factors affecting cellular radiosensitivity?

Answer 26

• Conditional factors
• Inherent factors

Question 27

___ includes those biologic factors that are characteristics of the cells themselves, such as the mitotic rate, the degree of differentiation, and the stage of the cell cycle

Answer 27

Inherent radiosensitivity

Question 28

___ are those physical or chemical factors that exist before and/or at the time of irradiation. Some of the more important ___ factors affecting dose-response relationships include dose rate, LET, and the presence of oxygen.

Answer 28

Conditional radiosensitivities

Question 29

In general, high dose rates are more effective at producing biologic damage than low dose rates. This dose-rate effect is diminished or not seen with ___-LET radiation primarily because the dense ionization tracks typically produce more complex, clustered DNA damage that cannot be repaired correctly. However, for a given dose rate, ___-LET radiation is considerably more effective in producing cell damage than low-LET radiation

Answer 29

high-LET radiation

Question 30

The presence of this molecule increases the damage caused by low-LET radiation by inhibiting the recombination of free radicals to form harmless chemical species and by inhibiting the chemical repair of damage caused by free radicals

Answer 30

Oxygen

Question 31

In 1906, these two French scientists experimented the relative radiosensitivity of rodent germ cells at different stages of spermatogenesis.

Answer 31

• J. Bergonie
• L. Tribondeau

Question 32

This law states that radiosensitivity is greatest for thos cells that (1) have a high mitotic rate, (2) have a long mitotic future, and (3) are undifferentiated.

Answer 32

The Law of Bergonie and Tribondeau

For example, the pluripotential stem cells in the bone marrow have a high mitotic rate, a long mitotic future, are poorly differentiated, and are extremely radiosensitive compared with other cells in the body. On the other end of the spectrum, the fixed postmitotic cells that comprise the central nervous system (CNS) are relatively radioresistant

Question 33

Arrange in order: most to least sensitive.

sperm, lymphocyte, hematopoeietic stem cells, small intestine crypt cells, hair follicles, colon and stomach, skin, kidney, CNS (Neurons), muscle, bone

Answer 33

Question 34

This classification scheme was refined in 1968 by Rubin and Casarett, who defined five cell types according to characteristics that affect their radiosensitivity

Answer 34

Question 35

Arrange in order: most to least sensitive to radiation

A. “gap” between S phase and Mitosis (G2)
B. Mitosis (M phase)
C. late DNA synthesis (S phase)
D. preperatory period for DNA synthesis (G1)

Answer 35

B. Mitosis (M phase)
A. “gap” between S phase and Mitosis (G2)
D. preperatory period for DNA synthesis (G1)
C. late DNA synthesis (S phase)

Question 36

An initial exposure or “priming dose” reduced the effectiveness of a subsequent exposure

Answer 36

Adaptive Response to radiation

Question 37

A fascinating phenomenon in which irradiated cells or tissues can produce deleterious effects on nonirradiated cells or tissues.

Answer 37

Bystander effect

Question 38

While the vast majority of unrepaired and misrepaired radiation-induced lesions are expressed as chromosomal damage at the first division, a certain fraction of cells can express chromosomal damage such as chromosomal rearrangements, chromatid breaks and gaps, and micronuclei over many cell cycles after they are irradiated. demonstrated in vitro as delayed lethality in which cell cloning efficiency is reduced several generations after irradiation.

Answer 38

Genomic Instability

Question 39

Concept

The response of an organ system to radiation depends not only on the dose, dose rate, and LET of the radiation but also on the relative radiosensitivities of the cells that comprise both the functional parenchyma and the supportive stroma.

Answer 39

Organ system response to Radiation

The response is measured in terms of morphologic and functional changes of the organ system as a whole rather than simply changes in cell survival and kinetics. The response of an organ system after irradiation occurs over a period of time. The higher the dose, the shorter the interval before the physiologic manifestations of the damage become apparent (latent period) and the shorter the period of expression during which the full extent of the radiation-induced damage is evidenced. There are practical threshold doses below which no significant changes are apparent. In most cases, the pathology induced by radiation is undistinguishable from naturally occurring pathology.

Question 40

This refers to replacement of the damaged cells in the organ by cells of the same type, thus replacing the lost functional capacity.

Answer 40

Regeneration

Question 41

Refers to the replacement of the damaged cells by fibrotic scar tissue, in which case the functionality of the organ system is compromised.

Answer 41

Repair

Question 42

True or False

The types of response and the degree to which they occur are functions of the dose, the volume of tissue irradiated, and the relative radiosensitivity and regenerative capacity of the cells that comprise the organ system.

Answer 42

True

Question 43

True or False

In radiation therapy, fractionation increases the effectiveness of the radiation by allowing for reoxygenation of the tumor cells and reassortment (redistribution) of the irradiated cells into more radiosensitive phases of the cell cycle.

Answer 43

True

Question 44

Although a relateive rare event, it is still the MOST COMMONLY encountered tisse reaction (deterministic effect) following high-dose image guided interventional procedures

Answer 44

Radiation-induced SKIN damage

Question 45

Skin reactions to radiation exposure are deterministic and have a threshold of approximately ___ Gy below which no effects are seen.

Answer 45

1 Gy

Question 46

There are often no immediate clinical symptoms from a high skin dose and when initial symptoms do develop, they are often delayed by weeks or even months. What are the symptoms?

Answer 46

erythema, xerosis, pruritus

Question 47

The reaction of skin to ionizing radiation

Answer 47

cutaneous radiation syndrome

Question 48

This inflammatory response is largely caused by increased capillary dilatation and permeability secondary to the release of vasoactive amines (e.g., histamine)

Answer 48

early transient erythema

Question 49

This is believed to be an inflammatory reaction secondary to release of proteolytic enzymes from damaged epithelial basal cells as well as reflecting loss of those epithelial cells.

Answer 49

Secondary or main erythema

Question 50

This may also be seen between between 8 and 52 weeks after exposure. The dermal ischemia present at this stage produces an erythema with a bluish or mauve tinge. Temporary hair los

Answer 50

third or late erythema

Question 51

___ can occur in approximately 3 weeks after exposure to 3 to 6 Gy, with regrowth beginning approximately 2 months later and complete within 6 to 12 months. After moderately large doses—40 Gy over a period of 4 weeks or 20 Gy in a single dose—intense erythema followed by an acute radiation dermatitis and moist desquamation occurs and is characterized by edema, dermal hypoplasia, inflammatory cell infiltration, damage to vascular structures, and permanent hair loss.

Answer 51

Epilation (temporary hair loss)

Question 52

___, which implies a total destruction of the epidermis, is a clear predictor of late delayed injuries, particularly telangiectasia.

Answer 52

Moist desquamation

Question 53

___ can also be produced by repeated low-level exposures (10 to 20 mGy/d) where the total dose approaches 20 Gy or more. In these cases the skin may become hypertrophic or atrophic and is at increased risk for development of skin neoplasms (especially squamous cell carcinoma). Erythema will not result from chronic exposures in which the total dose is less than 6 Gy.

Answer 53

Chronic radiation dermatitis

Question 54

Radionuclides with high specific activity and high-energy beta particle emissions such as ___ are more likely to illicit skin reactions

Answer 54

F-18 radionuclide

Question 55

most radiosensitive: ___
Intermediate:___
most radioresistant:___

Answer 55

• most radiosensitive: spermatogonia
• Intermediate: 1 & 2 spermatocytes and spermatids
• most radioresistant: mature spermatozoa

Question 56

Temporary sterility can occur after acute doses of approx ___ mGy

The duration of temporary sterility is dose dependent with recovery beginning at 1 and as long as 3.5 years after doses of 1 and 2 Gy, respectively. However, following exposure (and provided the dose is not excessive), there will be a window of fertility before the onset of sterility, as long as mature sperms are available.

Answer 56

500 mGy

Question 57

Permanent sterility can occur after acute doses of approx ___ Gy

Answer 57

6 Gy

Question 58

Chronic exposures of ___ mGy/wk can result in permanent sterility when total dose exceeds ___ Gy

Answer 58

Chronic exposures of 20 to 50 mGy/wk can result in permanent sterility when total dose exceeds 2.5 to 3 Gy

Question 59

Reduced fertility due to decreased sperm count (oligospermia) and motility (asthenozoospermia) can occur 6 weeks after a dose of ___ mGy

Answer 59

150 mGy

Question 60

The ova within ovarian follicles are sensitive to radiation. Arrange the following in order of most to least radiosensitive: small, intermediate, large follicles.

Answer 60

Intermediate follicles -> large (mature) follicles -> small follicles

Question 61

In women, permanent sterility is age dependent.
prior to puberty: 10 Gy
premenopausal: (over 40 yo): 2 to 3 Gy

Answer 61

prior to puberty: 10 Gy
premenopausal: (over 40 yo): 2 to 3 Gy

Question 62

The ___ of the eye contains a population of radiosensitive cells that can be damaged or destroyed by radiation.

Answer 62

Lens

Question 63

A unique aspect of cataract formation is that, unlike senile cataracts, which typically develop in the ___ pole of the lens, radiation-induced cataracts are caused by abnormal differentiation of damaged epithelial cells that begin as a small opacities (abnormal lens fibers) in the ___ ___region and migrate posteriorly.

Answer 63

Senile cataract : anterior pole of lens

Radiation induced cataracts: anterior subcapsular region and migrate posteriorly

Question 64

Dose thresholds for detectable opacities?

Answer 64

acute exposure: 2 Gy
chronic exposure: 5 Gy

Question 65

Occupational equivalent dose limit for the lens of the eye

Answer 65

(20 mSv/y averaged over 5 years, with no single year exceeding 50 mSv)

Question 66

When the whole body (or large portion of the body) is subjected to a high acute radiation dose, there are a series of characteristic clinical responses known collectively as the ___ ?

The ARS refers to a group of subsyndromes occurring in stages over a period of hours to weeks after the exposure as the injury to various tissues and organ systems is expressed. These subsyndromes result from the differing radiosensitivities of these organ systems

Answer 66

acute radiation syndrome (ARS)

Question 67

How do you divide (in order of occurence with increasing radiation dose ARS?

Answer 67

Hematopoietic
Gastrointetinal
Neurovascular

Question 68

ARS can occur when a high radiation dose is ___, ___ and ___.

Answer 68

1. delivered acutely
2. involves exposure to the whole body (or at least a large portion of it)
3. is from external penetrating radiation (xray, gamma ray, neutron)

Question 69

What is the sequence of events in ARS?

Answer 69

prodromal, latent, manifest illness, recovery/death

Question 70

As the whole-body exposure increases above a threshold of approximately ___ Gy, the prodromal symptoms, which (depending on dose) can include anorexia, nausea, lethargy, fever, vomiting, headache, diarrhea and altered mental status, begin earlier and are more severe.

Answer 70

0.5 to 1 Gy

Question 71

The prodromal symptoms subside during the ___, whose duration is shorter for higher doses and may last for up to 4 weeks for modest exposures less than 1 Gy. The latent period can be thought of as an “incubation period” during which the organ system damage is progressing.

Answer 71

Latent period

Question 72

The latent period ends with the onset of the clinical expression of organ system damage, called the ___, which can last for approximately 2 to 4 weeks or in some cases even longer. This stage is the most difficult to manage from a therapeutic standpoint, because of the overlying immunoincompetence that results from damage to the hematopoietic system.

Answer 72

manifest illness stage

Therefore, treatment during the first 6 to 8 weeks after the exposure is essential to optimize the chances for recovery. If the patient survives the manifest illness stage, recovery is likely;

Question 73

The hematopoietic syndrome is the primary acute clinical consequence of an acute radiation dose between ___ and ___ Gy. Healthy adults with proper medical care almost always recover from doses lower than ___ Gy, whereas doses greater than ___ Gy are almost always fatal

Answer 73

between 0.5 and 10 Gy

lower than 2 Gy

greater than 8 Gy

Question 74

____ radiation exposure maximizes damage because the majority of the active bone marrow is located in the spine and posterior region of the ribs and pelvis.

Answer 74

Posterior

Question 75

Even with effective stem cells therapy, however, it is unlikely that patients will survive doses in excess of ___ Gy because of irreversible damage to the gastrointestinal tract and the vasculature.

Answer 75

12 Gy

Question 76

In the absence of medical care, the human LD50/60 (the dose that would be expected to kill 50% of an exposed population within 60 days) is approximately ___ Gy to the bone marrow.

Answer 76

3.5 to 4.5 Gy

Question 77

The decline in the ___ count occurs within hours after exposure and is a crude early biologic marker of the magnitude of exposure. The threshold for a measurable depression in the blood lymphocyte count is approximately ___ Gy; an absolute lymphocyte count lower than 1,000/mm3 in the first 48 hours indicates a severe exposure.

Answer 77

lymphocyte count
0.25 Gy

Question 78

The clinical manifestation of bone marrow depletion peak ___ weeks after the exposure as the number of cells in circulation reaches its nadir.

Answer 78

3 to 4 weeks

Question 79

Lethal consequences of severe hematopoietic compromise?

Answer 79

Hemorrhage from plt loss and opportunistic infection due to severe neutropenia

Question 80

At higher doses, this becomes the dominant expression of radiation response with more immediate, severe consequences that overlap with hematopoietic syndrome. At doses higher than ___ Gy, is primarily responsible for lethality.

Answer 80

Gastrointestinal syndrome; 12 Gy

Question 81

Its prodromal stage includes severe nausea, vomiting, watery diarrhea, and cramps occurring within hours after the exposure, followed by a much shorter latent period (5 to 7 days). The manifest illness stage begins with the return of the prodromal symptoms that are often more intense than during their initial presentation. The intestinal dysfunction is the result of the severe damage to the intestinal mucosa.

Answer 81

Gastrointestinal syndrome

Question 82

Its most potentially serious effect is the severe decrease in circulating white cells at a time when bacteria are invading the bloodstream from the gastrointestinal tract.

Answer 82

Gastrointestinal syndrome

Question 83

Systemic effects of acute radiation enteropathy

Answer 83

• malnutrition resulting from malabsorption; vomiting and abdominal distention from paralytic ileus; anemia from gastrointestinal bleeding; sepsis resulting from invasion of intestinal bacteria into the systemic circulation; and dehydration and acute renal failure from fluid and electrolyte imbalance.

Question 84

Lethality from the gastrointestinal syndrome is essentially ___%. Death occurs within 3 to 10 days after the exposure if no medical care is given or as long as 2 weeks afterward with intensive medical support.

Answer 84

100%

It is important to appreciate that even at doses within the hematopoietic syndrome dose range (2 to 10 Gy), damage to the gastrointestinal tract is occurring. It is responsible for many of the prodromal symptoms and contributes to the toxicity of the radiation-induced myelosuppression that is the signature of the hematopoietic component of the ARS. While a whole body dose of 6 Gy does not result in the full gastrointestinal sequelae described above, damage to the mucosal barrier causes cytokines and other inflammatory mediators to be released into the circulation.

Question 85

In this syndrome, death occurs within 2 to 3 days after supralethal doses in excess of ___ Gy.

Answer 85

Neurovascular syndrome; 50 Gy

Question 86

In this syndrome, period may include a burning sensation of the skin that occurs within minutes, followed by nausea, vomiting, confusion, ataxia, and disorientation within 1 hour. There is an abbreviated latent period (4 to 6 hours), during which some improvement is noted, followed by a severe manifest illness stage. The prodromal symptoms return with even greater severity, coupled with respiratory distress and gross neurologic changes (including tremors and convulsions) that inevitably lead to coma and death.

Answer 86

Neurovascular syndrome

Question 87

What are the three stages of gestational period?

Answer 87

1. Preimplantation
2. Organogenesis
3. Fetal growth stage

Question 88

This stage begins with the union of the sperm and egg and continues through day 9 in humans, when the zygote becomes embedded in the uterine wall The conceptus is very sensitive during the preimplantation stage and susceptibility to the lethal effects of irradiation is a concern. However, for doses less than ___ mGy, the risks are very low.

Answer 88

Preimplantation stage; less than 100 mGy (low risk)

Question 89

In preimplantation period, embryos exhibit this response to radiation exposure in which if the exposure is not lethal, the damaged cells are repaired or replaced to the extent that there is unlikely to be any additional radiation-induced risk of congenital abnormalities beyond that which would occur for other reasons

Answer 89

All-or-nothing response

Question 90

The most sensitive times of exposure in humans are at ___ hours after conception, when the two pronuclei fuse to the one-cell stage, and again at 30 and 60 hours when the first two divisions occur.

Answer 90

12 hours after conception

Question 91

After implantation doses in excess of ___ mGy are required to induce prenatal death.

Answer 91

250 mGy

Question 92

Embryonic malformations occur more frequently during the period of major organogenesis (___ to ___ week after conception).

Answer 92

2nd to 8th week after conception

Question 93

The initial differentiation of cells to form certain organ systems typically occurs on a specific gestational day.

neuroblasts: ___ gestational day
forebrain and eyes: ___ day
primitive germ cells: ___ day

Answer 93

neuroblasts: 18th gestational day
forebrain and eyes: 20th day
primitive germ cells: 21st day

Question 94

This the greatest probability of a malformation in a specific organ system to exist when radiation exposure is received during period of peak differentiation

Answer 94

Critical period

Question 95

The only organ system (in humans or laboratory rodents) that has shown an association between malformations and low-LET radiation doses less than 250 mGy

Answer 95

CNS

Embryos exposed early in organogenesis exhibit the greatest intrauterine growth retardation, presumably because of cell depletion. In utero exposure to doses greater than 100–200 mGy of mixed neutron and gamma radiation from the Hiroshima atomic bomb resulted in a significant increase in the occurrence of microcephaly.

Question 96

true or false

Radiation exposure of the embryo at the preimplantation stage usually leads to an allor-nothing phenomenon (i.e., either fetal death and resorption or normal fetal risk).

Answer 96

True

Question 97

True or false

During the period of organogenesis, the risk of fetal death decreases substantially, whereas the risk of congenital malformation coincides with the peak developmental periods of various organ systems. Exposures in excess of 1 Gy are associated with a high incidence of CNS abnormalities. During the fetal growth stage in utero, exposure poses little risk of congenital malformations; however, growth retardation, abnormalities of the nervous system, and the risk of childhood cancer can be increased depending on fetal dose.

Answer 97

True

Question 98

True or false

The ACR policy states “The interruption of pregnancy is rarely justified because of radiation risk to the embryo or fetus from a radiologic examination.” (ACR, 2005). The ACOG policy, which was revised in 2004, states “Women should be counseled that x-ray exposure from a single diagnostic procedure does not result in harmful fetal effects. Specifically, exposure to less than 5 rad [50 mGy] has not been associated with an increase in fetal anomalies or pregnancy loss.” (ACOG, 2004).

Answer 98

True