Radiobiology Flashcards
LET
Linear Energy Transfer
RBE
Relative Biological Effectiveness
OER
Oxygen Enhancement Ratio
What is LET defined as?
Rate at which energy is deposit as charge particles travel through matter
What is High LET and characteristic of the particles that provide this effect?
Particulate Radiation and Mass, Charged particles, short distance and densely ionizing (Straight Path)
What is Low LET and characteristic of the particles that provide this effect?
Electromagnetic Radiation and No Mass/Charge, Travel at the speed of light and Sparsely Ionizing (Spiratic Path)
What is the the difference in biological effects compared to physic effects?
Biological effects take time as their process of reaction is significantly slower when compared to physics processes
What are compounds that undergo particulate interactions (High LET)?
Alpha, Beta, Electron and protons (Neutrons also undergo this process despite no charge or mass)
What are compounds that undergo electromagnetic interactions (Low LET)?
Xrays and Gamma rays
Alpha Particles
High Ionizing Density (Highest LET), +2 Charge, He nuclei
Neutron Particles
High Ionizing Density (2nd Highest LET), No Charge
Beta Particles
E- or Positrons (- or +), Low ionization density
X ray and Gamma Rays
Photons, Low ionization Density, High penetrating Power
Direct Action
Direct interaction of the radiation with the DNA, Pre-dom with High LET,
Indirect Action
Indirect interaction of the Radiation that interacts through a medium such as water, Pre-dom with Low LET
What happens to the survival curve as LET increases from X-rays to Alpha particles?
As the LET increases the curves begins to become steeper and the shoulder decreases in size
Indirectly Ionizing
High Energy, Small Wavelength, Large Frequency (Xrays and Gammas)
Relative Biological Effectiveness
Dose in Gy from a 250 Kv Xray divided by the dose in Gy of another radiation that has the same effect
How does RBE change with LET?
As LET increases, the RBE becomes more likely to increase the Damage and create cell overkill
What LET causes Cell kill?
100 KeV/um
Hypoxic
Oxygen depleted
Aerobic
Oxygen Rich
How do you find the OER?
Hypoxic/Aerobic
What occurs with more oxygen within the cell?
More oxygen within the cell will create an environment in which free radicals are more frequently occurring increase the damage to the cell
What the relationship with OER and survival curves?
Those radiations that have lower OER exhibit survival rates that are more steeper compared to the those that have high OER (More Densely ionizing= Lower OER= Steeper survival curve)
What is the relationship with OER and RBE, when looking at LET?
Inverse relationship, High LET do not have a desire for High OER, which then creates a high RBE, Low LET desire do not desire a LOW OER which creates a Low RBE
What are the effects of radiation on DNA?
Hydrogen Bond, Loss of Base, Single strand break, Double strand break, Cross-links
What is the most deadly Radiation induced effect on DNA?
Double strand break
What is the Radiation induced effect on DNA is two independent events?
Cross-link
What are the 4 chromosomal Abberrations?
Deletion, Duplication, Inversion and Translocation
Explain Translocation chromosomal aberration?
The strands exchange information and create a new sequence of information
What are 3 lethal chromosome configurations?
Ring, Dicentric and Anaphase Bridge
Explain the ring chromosome configuration
Chromosomes have broken segments of deleted genetic material and then fusion between the two original chromosomes occurs, creating a ring
Dicentric vs Acentric Fragmentation
Chromosomes that are irradiated break, to which fusion between the broken arms occurs and you create a Dicentric fragment (Large fragment with double centromeres) or Acentric fragment (Small fragment with no centromere)
What is the cellular response to being irradiated?
Division Delay, Interphase Death or Productive Failure
What occurs during division delay in the response to radiation?
Delay in mitosis or recovery, Mitotic overshoot
What occurs during interphase death in the response to radiation?
Apoptosis, Cell line dependent, radiosensitive cells die at lower doses
What occurs during reproductive failure in the response to radiation?
cell fail to undergo repeated division, (Dose increase creates reproductive failure)
In vivo
In living organism
In vitro
In glassware or artificial environment
What two factors are considered in cell survival curves?
Survival vs. Dose
How do you find plating efficiency?
Colonies counted/ # cells seeded
How do you find Survival Fraction?
of colonies counted/ # of cells seeded x Plating efficiency
Who are Puck and Marcus?
Created the first studies done on cell survival curves for radiation
What are the 3 cell parameters measured on survival curves?
n, Dq and Do
What is n?
Extrapolation # (Width of shoulder)
What is Dq?
Quasi-threshold (Width of shoulder region)
What is Do?
Radio-sensitivity (Measure of cell survival
What is the extrapolation number?
Extrapolate exponential portion back to Y-axis and number of targets to be hit to cause cell death (2-10 mammalian)
What is the quasi-threshold dose?
Terminal portion of curve intercepts dose axis at 100%, represents SF= 1 so a 100% survival
What is the Radiosensitivity variable, Do?
Reciprocal of Slope, dose that inactive all but 37% of population (1-2 Gy for mammalian)
What does a higher Do mean?
More resistant
What would a survival curve for a low Do look like?
Steeper, with a Lower Do, the radiosensitive is higher for lower dose creating a survival curve with a more drastic result
Higher LET= _______ in survival?
Decrease, more damaging, less likely chance of survival
What occurs to the survival curve as the LET gets higher?
Steeper and Lower Do as the dose to immobilize the majority of the population lowers
If given the option to choice between G2 and M, in regards to which is most radiosensitive, which would be the better answer?
M
What are the three types of damage that can occur to cells?
Lethal, Sublethal and Potentially Lethal Damage
What are the three SSSs of sublethal damage?
Sublethal, Split Fx, and Shoulder
How was potentially lethal damage originally studied?
Irradiated cells were placed in suboptimal cell division conditions
What was the result of studying potentially lethal damage?
Survival increased for the irradiated cells in suboptimal conditions as they were not forced to undergo cell division compared to those that are forced to in optimum conditions, requires 6-12 hours
Radio-sensitivity is directly proportional to? Indirectly proportional to?
Directly proportional to reproductive activity and indirectly proportional to degree of differentiation
More Reproductive cells = _________ radio-sensitive ?
More
Least Differentiation= _______ Radiosensitive?
More
What are the classification of cells based on radiosensitive?
VIM, DIM, Multi-potential, RPM and FPM
VIM
Vegetative inter-mitotic, rapidly dividing, undifferentiated
DIM
Differentiation Inter-mitotic, Actively dividing
RPM
Reverse Post-mitotic, not normal dividing, variably differentiated
FPM
Fixed Post-mitotic, do not divide highly differentiated
What is the most sensitive cell classification?
VIM
What is the least sensitive cell classification?
FPM
Multipotential Connective Tissue
Irregularly dividing
Example of VIM
Erythoblast
Example of Multipotential Connective Tissue
Spermatocyte
Example of FPM
Nerve Cell
Radiosensitizers
Increase response to radiation, (Ex: Oxygen)
Radioprotectors
Decrease response to radiation, protection of Dose limiting structures
What is the best radiosensitizer?
Oxygen
When is oxygen give to patients for their treatment?
Administered during treatment
What is acute responding tissue?
Tissue rxn within few months after XRT, Rapidly dividing organs (Intestine, Bone Marrow, Testes)
What is late responding tissue?
Tissue rxn greater than 3 months post xrt, slow dividing organs (Lung and Kidney)
What is the LD 50/30?
Dose to produce lethality to 50% of the population in 3o days (LD 50/60 for humans)
What is the LD 50/30 for humans?
3.5-4.5 Gy
Acute radiation Syndrome 3 area affected
Hematopoietic, Gastrointestinal, CNS/CV
Hematopoietic (Bone Marrow)
2-10 Gy, infection and hemorrhaging, 6 weeks to 6 days survival avg , dose dependent (Lowers chances of survival)
Gastrointestinal (ARS)
10-100 Gy, Small intestine damaged, No survival, 3-10 days survival avg, no dose dependent
CNS/CV (ARS)
> 100 Gy, Cerebral Edema, no Survival, 2-3 day survival avg, Dose Dependent (Lowers chances of survival)
What is the LD 50/60 for ARS?
400 cGy
What are the specific conditions to induce ARS?
Acute exposure (within minutes), Area exposed is total body, Exposure to external penetrating sources
Whats different about internal deposition and inducing full ARS syndrome?
internal Radioactive materials do not induce full syndrome
What are some ARS scenarios that have occurred “Naturally”
Hiroshima/Nagasacki and Chernobyl
What are the 4 stages of ARS?
Prodromal, Latent, Manifest Illness, Recovery/death
What happens to the stages of ARS as severity increases?
The stages decrease in time
Prodromal
Initial stage, N/V and Diarrhea,Minutes to Days
Latent
no symptoms, healthy looking, weeks down to hours
Manifest Illness
Symptoms return, obvious illness, Exhibit specific symptoms, min to weeks
What are the two types of radiation effects?
Stochastic and Deterministic
Stochastic Effects
no threshold, no dose dependent, higher dose creates higher chance of expecting results (Cancer, Herediatary effects)
Deterministic Effects
Threshold, Severity is dose dependent, Higher dose creates higher change of expecting results (Cataracts, Skin injuries)
What is another name for late effects?
Somatic
Somatic Effects
Non-specific Life shortening, Carcinogenesis, Cataractogenesis, Embryo/fetus effects
Non-specific life shortening
Radiation-inducing aging, shortened life span, those chronically exposed will die before those that weren’t
Carcinogenesis
SINGLE MOST IMPORTANT LATE SOMATIC EFFECT, Marie Curie died due to working with radiation unsafely
What is the latency period for leukemia?
5-7 years, absolute risk
What is the latency period for solid cancers?
20-60 years, relative risk
six solid radiation inducing cancers?
Skin, Bone, Breast, Lung, and Thyroid
Cataractogenesis
Deterministic effect, Threshold of 2 Gy (Stationary 2-6 Gy, Progressive 6-12 Gy)
Embryonic and Fetal
Dose and age of gestation dependent,
3 stages of embryonic and fetal impact?
Prenatal, Major organogenesis, Fetal
Prenatal
0-9 days, prenatal death
Major organogenesis
10-42 days, Congenital abnormalities and neonatal death
Fetal
> 6 weeks - term, Functional abnormalities
Hereditary Effects
Genetics based, Double dose- 1 Gy,
What is the genetic counseling recommendation for conceptions post xrt?
6 months
True or False. Radiation produced new mutations and also increases an already existing number.
False, Radiation does not create any new mutations, only increase the already existing ones
Fractionation
Multifraction regime that produces better tumor control for given level of normal tissue toxicity than a single large dose
What are the 4 R’s of Radiobiology?
Repair, Repopulation, Reassortment and Reoxygenation
1st R, Repair
repair of sublethal damage between dose fraction
2nd R, Repopulation
cell repopulate if given appropriate amount of time
3rd R, Reassortment
Cycling cells into sensitive phases of the cell cycle
4th R, Reoxygenation
enhance cell kill
Acute tumor hypoxia
Low oxygen concentration, temporary closing or blocking of blood vessels
Chronic tumor hypoxia
Peristent low oxygen concentration, exist in viable tumor cells close to necrosis
Normoxic
Normal oxygen concentration
Dose-Response Relationships
Radiation Biology applied to Clinical radiotherapy is concerned with the relationship b/w a given absorbed dose of radiation and the consequent biologic response
With increasing radiation dose, effects may increase in ______ in ____ or both?
Severity (grade) and Frequency (Incidence)
Therapeutic ratio
percent of tumor control achieved for given level of normal tissue damage
Therapeutic ratio factors (____/_____)
Tumor control probability/Normal Tissue Complication Probability
In regards to therapeutic window, the further apart the curves creates what?
A larger therapeutic window
Law of Bergonie and Tribondeau
Mitotic Activity and Differentiation
Rubin and Casarett
Radiosensitivity
Tolerance Dose
dose the produced an acceptably probability of treatment complications (TD 5/5 and TD 50/5)
Emami provides?
TD for 1/3, 2/3, and whole organ with clinical endpoint
QUANTEC provides?
Dmax, Mean dose, Dose/volume parameters
TD 5/5
Dose which when given to population will result in a minimum 5% several complication rate within 5 years
TD 50/5
Dose which when given to population will result in a maximum 50% several complication rate within 5 years
Early Responding Tissue (VIM, DIM)
Rapidly dividing cells, (Skin, Bone Marrow, Intestinal lining and testes)
Late responding Tissue (RPM FPM)
Slowly dividing cells (Lung,CNS, Kidney, Liver)
What dose QUANTEC stand for?
Quantitative analyses of normal tissue effects in the clinic
