AIM: Ch 20: Radiation Biology Flashcards
Biologic effects of radiation exposure in which the probability of the effect occurring, (rather than its severity), increases with dose
Stochastic effect
-NO dose threshold: damage to a few cells or even a single cell could theoretically result in production of the disease
Stochastic versus deterministic effect:
a. Radiation-induced cancer
b. Hereditary effects
c. Skin erythema
d. Fibrosis and hematopoietic damage
a-b. Stochastic effects
c-d. Deterministic effects
Effects in which the severity of the injury, (rather than its probability of occurrence), increases with dose
Deterministic effects
aka tissue reactions
WITH threshold dose
The delta rays and other lower energy electrons, set in motion following an initial ionizing event, result in a unique ionization pattern in which closely spaced ionizations occur over a very short range (~4 to 12 nm) along the path of the primary ionization track. The energy deposition (~100 ev) along the shorter tracks referred to as ____
Spurs
Diameters are approximately 4 to 5 nm, result in an average of three ionizing events
It is estimated that 95% of the energy deposition events from x-rays and gamma rays occurs in spurs
Longer and less frequent pear shaped tracks called ____ deposit more energy (~300 to 500 ev) and thus on average result in more ionization events (~12 ion pairs) over their path (~12 nm)
Blobs
If ionizing events occur near the DNA, whose diameter (~2 nm) is on the same order as that of these short ionization tracks, they can produce damage in multiple locations in the DNA in close proximity to one another. These lesions are called ____
Locally multiply damaged sites
These are more difficult for the cell to repair or may be repaired incorrectly
Synonyms for this type of damage in more common use today include clustered damage, complex damage, and multiply damaged sites (MDS).
While endogenous processes mainly produce isolated DNA lesions, the complex clustered damage, in which groups of SEVERAL damaged nucleotides occur within ONE or TWO helical turns of the DNA, is a HALLMARK of ionizing radiationinduced DNA damage.
It would take more than ____, a supralethal dose, to raise the temperature of tissue by 1°C.
4,000 Gy
Only a fraction of the radiation energy deposited brings about chemical changes; the vast majority of the energy is deposited as heat. The heat produced is of little biologic significance compared with the heat generated by normal metabolic processes.
Radiation interactions that produce biologic changes are classified as either direct or indirect.
The change is said to be due to ____ action if a biologic macromolecule such as DNA, RNA, or protein becomes ionized or excited by an ionizing particle or photon passing through or near it.
____ action refers to effects that are the result of radiation interactions within the medium (e.g., cytoplasm) that create mobile, chemically reactive species that in turn interact with nearby macromolecules
Direct
Indirect
These are denoted by a dot next to the chemical symbol, and are atomic or molecular species that have unpaired orbital electrons
Free radicals
Thus, free radicals can be radical ions (e.g., H2O+ and H2O-), or electrically neutral (∙OH). The hydrogen and hydroxyl radicals can be created by other reaction pathways, the most important of which is the radiation-induced excitation and disassociation of a water molecule (H2O* excitation → H∙ and ∙OH)
Primary cause of biologic damage from low-LET radiation
Free radical-induced damage to DNA
While radiation exposure from medical imaging does result in some direct ionization of critical cellular targets, approximately two thirds of the total radiation damage is due to the free radical-mediated indirect effects of ionizing radiation.
It is a parameter that describes the average energy deposition per unit path length of the incident radiation
LET
The term relating the effectiveness of the test radiation to the reference radiation is called the ____
Relative biological effectiveness (RBE)
It refers to the deposition of radiation energy in excess of that necessary to produce the maximum biologic effect.
Overkill (or wasted dose)
The RBE is an essential element in establishing the radiation weighting factors (wR)
There is considerable evidence that damage to ____ is the primary cause of radiation-induced cell death.
DNA
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 including the following, except:
a. Hydrogen bond breakage
b. Molecular degradation or breakage
c. Intermolecular and intramolecular cross-linking
d. All of the above are part of the said structural changes
d. AOTA
The increased effectiveness of alpha particles in producing biological damage is not due to an increased yield of DNA damage but rather the ability of the higher ionization density to produce more complex DNA lesions (Brenner and Ward, 1992). This ability to produce several MDS in proximity in the chromatin structure is referred to as ____
Regional multiply damaged sites (RMDS)
Chromosomal damage that occurs before DNA replication is referred to as ____, whereas that occurring after DNA synthesis is called ____
Chromosome aberrations
Chromatid aberrations
BEFORE: ChromOsomes
AFTER: ChromAtid
Chromosome breaks produced by radiation do occur and can be observed microscopically during ____ and ____, when the chromosomes are condensed
Anaphase, metaphase
DNA damage induces several cellular responses that enable the cell either to repair or to cope with the damage. For example, the cell may activate the ____ (which arrests cell cycle progression), to allow for repair of damaged or incompletely replicated chromosomes
G1/S checkpoint
It detects the damaged base and removes it, creating an abasic site
DNA glycosylase
It joins the DNA segments
DNA ligase
Most DNA base damage and SSBs are repaired by the ____
Base excision repair pathway
It is the major pathway for the repair of bulky, helix-distorting lesions such as thymine dimers produced by exposure to ultraviolet radiation
Nucleotid excision repair
(NER)
More persistent, stable reciprocal translocations can be measured using ____
Fluorescence in situ hybridization (FISH)
While a wide variety of the biologic responses to radiation have been identified, the study of radiation-induced reproductive failure (also referred to as ____) is particularly useful in assessing the relative biologic impact of various types of radiation and exposure conditions
Clonogenic cell death or loss of reproductive integrity
T/F: For differentiated cells that no longer have the capacity for cell division (e.g., muscle and nerve cells), cell death is often defined as loss of specific metabolic functions or functional capacity.
True
It describes the radiosensitivity of the cell population under study. It is the reciprocal of the slope of the linear portion of the survival curve, and it is the dose of radiation that produces, along the linear portion of the curve, a 37% reduction in the number of viable cells
D0
Radioresistant cells have a higher D0 than radiosensitive cells. A lower D0 implies less survival per dose. The D0 for mammalian cells ranges from approximately 1 to 2 Gy for low LET radiation.
This component of the survival curve represents the damage done by individual radiation particle tracks and is thus independent of dose rate. While the damage is partially repairable over time, this still represents the probability of cell death due to individual, noninteracting, particle tracks.
Linear (alpha) component of the survival curve
This linear (single-hit kinetics) dose-response relationship dominates with high-LET radiation
This component of the survival curve represents the probability of cell death due to interactions between two or more individual particle tracks (i.e., dominates with low-LET radiation and follows multiple-hit kinetics) causing the curve to bend at higher doses and is sensitive to dose rate
Quadratic (beta) component of the survival curve
The dose at which cell killing is equal from the linear (aD) and quadratic (bD2) contribution is referred to as the ____. It is a measure of the curvature of the cell survival curve and, thus, a measure of the sensitivity of different cell types to fractionation of radiation dose
a/b ratio
Cellular radiosensitivity can be influenced by a variety of factors that can enhance or diminish the response to radiation or alter the temporal relationship between the exposure and a given response. Those physical or chemical factors that exist before and/or at the time of irradiation are called ____
Conditional radiosensitivities
Include: dose rate, LET, and the presence of oxygen
Cellular radiosensitivity can be influenced by a variety of factors that can enhance or diminish the response to radiation or alter the temporal relationship between the exposure and a given response. The factors that include 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, are called ____
Inherent radiosensitivity
The relative effectiveness of radiation to produce damage at various oxygen tensions is described by the ____.
Oxygen enhancement ratio (OER)
It is defined as the dose of radiation that produces a given biologic response in the absence of oxygen divided by the dose of radiation that produces the same biologic response in the presence of oxygen
Increasing the oxygen concentration at the time of irradiation has been shown to enhance the killing of otherwise hypoxic (i.e., radioresistant) cells that can be found in some tumors.
It states that radiosensitivity is greatest for those cells that (1) have a high mitotic rate, (2) have a long mitotic future, and (3) are undifferentiated.
Law of Bergonie and Tribondeau
Top 3 most sensitive cells
Spermatogonia
Lymphocytes, oocytes
Hematopoietic cells
Top 3 least sensitive cells
Bone
Muscle
CNS (neurons)
The following cells do not divide or are differentiated and are classified as fixed postmitotic cells, except:
a. Some nerve cells
b. Erythrocytes
c. Spermatozoa
d. Bone
d. Bone
The following cells are rapidly dividing; undifferentiated; do not differentiate between divisions, and are therefore radiosensitive, except:
a. Type A spermatogonia
b. Erythrocytes
c. Crypt cells of intestines
d. Basal cells of epidermis
b. Erythrocytes
Cells are most sensitive to radiation during ____ and ____
Mitosis (M phase)
“Gap” between S phase and mitosis (G2)
Cells are least sensitive during ____
Late DNA synthesis (S phase)
It refers to replacement of the damaged cells in the organ by cells of the same type, thus replacing the lost functional capacity
Regeneration
It refers to the replacement of the damaged cells by fibrotic scar tissue, in which case the functionality of the organ system is compromised
Repair
Skin reactions to radiation exposure are deterministic and have a threshold of approximately ____ below which no effects are seen.
1 Gy
A generalized erythema can occur within hours following an acute dose of 2 Gy or more of low-LET radiation and will typically fade within a few hours or days. This inflammatory response, often referred to as ____, is largely caused by increased capillary dilatation and permeability secondary to the release of vasoactive amines (e.g., histamine)
Early transient erythema
A later wave of erythema can reappear as early as 2 weeks after a high initial exposure or after repeated lower exposures (e.g., 2 Gy/ day as in radiation therapy), reaching a maximal response about the third week, at which time the skin may be edematous, tender, and often exhibit a burning sensation. 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
Secondary or main erythema
A third or late erythema wave may also be seen between between ____ after exposure. The dermal ischemia present at this stage produces an erythema with a bluish or mauve tinge.
8 and 52 weeks
Temporary hair loss (epilation) can occur in approximately 3 weeks after exposure to ____, with regrowth beginning approximately 2 months later and complete within 6 to 12 months
3 to 6 Gy
Moist desquamation, which implies a total destruction of the epidermis, is a clear predictor of late delayed injuries, particularly telangiectasia.
Erythema will not result from chronic exposures in which the total dose is less than ____
6 Gy
ICRP’s recent review of the scientific evidence regarding the risk of radiation-induced cataract has led the commission to propose a much more conservative occupational equivalent dose limit for the lens of the eye (____ averaged over 5 years, with no single year exceeding ____)
20 mSv/y, 50 mSv
Posterior subcapsular cataract
This subsyndrome is dose dependent and can begin within minutes to hours after the exposure. As the whole-body exposure increases above a threshold of approximately 0.5 to 1 Gy, the symptoms, which (depending on dose) can include anorexia, nausea, lethargy, fever, vomiting, headache, diarrhea and altered mental status, begin earlier and are more severe
Prodromal stage
The prodromal symptoms subside during this period, whose duration is shorter for higher doses and may last for up to 4 weeks for modest exposures less than 1 Gy. This period can be thought of as an “incubation period” during which the organ system damage is progressing
Latent phase
The following are included among the most frequent radiation-induced cancers, except:
a. Female breast cancer
b. Skin cancer
c. Thyroid cancer
d. Leukemia
b. Skin cancer
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 is the ____
CNS
During this period the occurrence of radiation-induced prenatal death and congenital anomalies is, for the most part, negligible, unless the exposures are exceptional high and in the therapeutic range
Fetal growth stage
Begins after the end of major organogenesis (day 50) and continues until term.
Anomalies of the nervous system and sense organs are the primary radiation-induced abnormalities observed during this period, which coincides with their relative growth and development
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.
The greatest sensitivity for radiation-induced mental retardation is seen between the 8th and 15th weeks, during which the risk for severe mental retardation (SMR) to the fetus is approximately 44% per Gy with a threshold for SMR of approximately ____ (ICRP, 2003a)
200 to 300 mGy
For those exposed before the 16th week, the incidence of microcephaly was proportional to the dose, from about ____, above which the decreased occurrence was presumably due to the increase in fetal mortality
100–200 mGy up to 1.5 Gy
Due to differences in the periods of rapid proliferation and radiosensitivity of the glial and neuronal cells, microcephaly can appear without SMR between 0 and 7 weeks whereas they appear together at 8 to 15 weeks and SMR can occur without microcephaly at 16 to 25 weeks.
Radiation dose of ____ received before birth increases risk for childhood cancer
10 mGy
