Radiation Biology Flashcards
Which phases of the cell cycle are cells most radioresistant and radiosensitive
- Resistant - late S - more repair by homologous recombinant than non-homologous end joining
- Sensitive - G2/M - chromatin compaction and poor repair competence
G1 - intermediate - open structure of DNA
Explain the graph
Survival curve - decline of survival with increasing dose
Direct and Indirect effects of Ionising Radiation on the Human Body
Direct action: a secondary electron interacts with the DNA to produce an effect.
Indirect action: a secondary electron interacts with a water molecule to produce a hydroxyl radical (OH-), which damages the DNA.
Example: In direct action, x-ray photon absorption leads to interaction with DNA.
Radiation Lesions in DNA
Radiation causes lesions in DNA such as single and double strand breaks, base damage, protein-DNA crosslinks, and protein-protein crosslinks.
The number of DNA lesions generated by irradiation is large, but the number leading to cell kill is small.
Example: Dsb play a critical role in cell killing.
Major types of DNA Repair
Enzymatic mechanisms of DNA repair include non-homologous end joining (NHEJ) and homologous recombination (HR) for double strand breaks.
NHEJ operates throughout the cell cycle and is error-prone. HR requires sequence homology and operates in late S or G2 phases.
Example: NHEJ repair dominates in G1/S-phases.
Damage recognition and signalling
Recognition of radiation damage involves ATM binding to DNA termini, activating CHK kinases and p53. This leads to G1 arrest to allow for DNA repair.
Apoptosis can also be initiated by p53 after irradiation in specific cell types.
Example: ATM kinase activity phosphorylates p53.
Consequences of unrepaired DNA damage: Chromosome damage
Unrepaired DNA damage can lead to mutations affecting base pairing, coding, transcription, and gene expression. Chromosome analysis methods can detect unrepaired DNA damage.
Aberrant chromosomes like rings, dicentrics, and translocations can arise from broken ends rejoining.
Example: Dicentric chromosomes have two centromeres.
Radiobiological definition of cell death
Cells are considered ‘killed’ by radiation if they lose reproductive integrity.
What is a dicentric chromosome?
An abnormal chromosome with two centromeres
Centromere - the center of the chromosome where microtubules attach during cell division
What are chromosome translocations?
Changes where a chromosome breaks and the pieces attach to other chromosomes
How are cells generally regarded as ‘killed’ by radiation?
If they have lost reproductive integrity, not by whether they physically survive in the population.
What are the mechanisms that can lead to loss of reproductive integrity in cells due to radiation?
Apoptosis, necrosis, mitotic catastrophe, or induced senescence (deterioration with age)
What is apoptosis?
Programmed cell death with a strong feature in embryological development and lymphocyte turnover
What is the gold standard for measuring the radiosensitivity of a cell population?
Retention of reproductive integrity or mitotic intactness i.e. the ability of a cell to undergo more than 5-6 cell divisions
How is cell survival calculated after irradiation?
By correcting for the ‘plating efficiency’ of unirradiated cells
What is the most common model used for survival curves in radiation biology?
The linear-quadratic model, fitted using a second-order polynomial, with the constants α and β describing the decline of survival with increasing dose
When do renewing cells in a growing population participate in the cell cycle?
When not resting in Go phase
Which cell cycle phase is most radioresistant?
Late S-phase
Which cell cycle phase is most radiosensitive?
G2/M
What does Relative Biological Effectiveness (RBE) take into consideration?
Both effective and equivalent dose and how they will affect a particular organ system
What helps explain radioresistance in G1?
Chromatin compaction
Chromatin compaction and poor repair competence (reduced enzyme access) could explain the high radiosensitivity in G2/M.
What is Relative biological effectiveness (RBE)?
Takes into consideration both effective and equivalent dose and how they will affect a particular organ system.
Comparison of effects of different types of radiation is expressed as relative biological effectiveness (RBE).
What is RBE defined as?
The ratio of doses of γ rays (Dγ-ray) and the test radiation (Dr) required to produce an equal amount of a particular biological effect.
A dose of 1 Gy of α particle produces a much larger amount of a chosen biological effect than 1 Gy of γ rays.
What is the ‘shoulder’ of a survival curve a reflection of?
The repair capacity of a cell population.
The ‘shoulder’ or the curvature of a survival curve is usually considered to be a reflection of the repair capacity of a cell population.
What are bystander effects in radiation biology?
Cells close to irradiated cells but not themselves exposed to radiation may exhibit damage similar to that caused by radiation.
Currently the literature on bystander effects remains controversial.
What is the oxygen enhancement ratio (OER) used for?
To determine the dose in hypoxia divided by the dose in air to achieve the same survival level.
Sensitization by oxygen has generally been explained by the oxygen fixation hypothesis.
What is the dose reduction factor (DRF) of cysteine or cysteamine in whole body irradiated mice?
1.8
In whole body irradiated mice, addition of cysteine or cysteamine is protective with a dose reduction factor (DRF) of 1.8.
