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Questions and Answers
In which phase of the cell cycle is DNA most susceptible to damage from radiation?
In which phase of the cell cycle is DNA most susceptible to damage from radiation?
What is a characteristic of the S phase that contributes to its relative resistance to radiation?
What is a characteristic of the S phase that contributes to its relative resistance to radiation?
During which phase of the cell cycle does interphase death occur following radiation exposure?
During which phase of the cell cycle does interphase death occur following radiation exposure?
Which statement best describes the sensitivity of the G1 phase to radiation?
Which statement best describes the sensitivity of the G1 phase to radiation?
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Why is DNA injury considered effectively 'fixed in place' during the M phase?
Why is DNA injury considered effectively 'fixed in place' during the M phase?
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During which phase of the cell cycle is a cell most sensitive to radiation?
During which phase of the cell cycle is a cell most sensitive to radiation?
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What type of cell death is characterized by the loss of the cell's ability to divide, while still maintaining metabolic activity?
What type of cell death is characterized by the loss of the cell's ability to divide, while still maintaining metabolic activity?
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What is the primary cause of instant cell death following high doses of radiation?
What is the primary cause of instant cell death following high doses of radiation?
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Which type of cell death is also known as interphase death?
Which type of cell death is also known as interphase death?
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What does the shoulder of a cell survival curve represent?
What does the shoulder of a cell survival curve represent?
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How does high LET radiation affect the shoulder of a cell survival curve?
How does high LET radiation affect the shoulder of a cell survival curve?
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What is a typical average LET value for photons?
What is a typical average LET value for photons?
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What is the key characteristic of high LET radiation?
What is the key characteristic of high LET radiation?
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Study Notes
Course Information
- Course title: MRD441: RADIATION BIOLOGY & SAFETY
- University: UNIVERSITI TEKNOLOGI MARA
Learning Outcomes
- Students should understand radiation damage to DNA.
- Students should differentiate between cell survival curves.
- Students should describe factors affecting cell survival.
- Students should describe acute radiation syndrome.
DNA Structure
- DNA is a double helix.
- The sides of the helix are made of sugar and phosphate.
- The rungs of the helix are made of nitrogenous bases: guanine, cytosine, thymine, and adenine.
DNA Damage
- Radiation can damage DNA.
- Damage can include: base and sugar damage, single-strand breaks, and double-strand breaks.
- Damage can also include double-strand break fragments
Common Causes of DNA Damage
- Replication stress
- Oxygen radicals
- Ionizing radiation
- Chemotherapy
- UV light
- Polycyclic aromatic hydrocarbons
DNA Repair Mechanisms
- Base excision repair (BER)
- Nucleotide excision repair (NER)
- Mismatch repair (MMR)
- Homologous recombination (HR)
- Non-homologous end-joining (NHEJ)
Cell Cycle
- Cell cycle is a series of phases a cell goes through.
- Phases include M, G1, S, G2, G0
- Mitosis (M) is a very sensitive phase to radiation.
- G1 is a resting phase that is moderately resistant to radiation
- S phase (DNA synthesis) is moderately resistant to radiation.
- G2 (resting phase) is sensitive to radiation.
- G0 are non-cycling cells and are moderately resistant to radiation.
Cell Cycle and Radiation Injury
- Mitosis: Chromosomes are condensed, DNA closely packed-bigger target, repair mechanisms are shut down, DNA injury is fixed in place, cells may loose large segments of DNA, fragments excluded from nucleus.
- S phase: DNA synthesis, most radiation resistant phase, cellular repair mechanisms are active, increases repair of radiation damage, lasts about 5 hours
- G1: functional part of cell cycle, resistance varies with part of phase, goes down as cell nears the G1-S interface, apoptosis occurs (cell death at this point is referred to as interphase death, longest part of cycle, lasts hours to years).
- G2: short rest phase before M, quite radiation sensitive, short time allows little injury repair, radiation injury incurred in S-phase may be repaired, may result in a mitotic delay in G2, apoptosis-like death may occur.
Cell Death
- Instant death: occurs when a volume is irradiated with 1000 Gray of x or gamma rays, in a period of seconds to minutes, energy absorbed by components, and causes DNA breakdown and coagulation of proteins
- Reproductive death: occurs from a dose of 1-10 Gray, the cell remains alive, but loses its capacity to divide.
Apoptosis
- Also known as interphase death
- Cell death before division.
Mitotic Death
- Occurs when the cell dies after one or more divisions.
- Can occur from very small doses.
- Cells exposed to radiation during division are most vulnerable to damage.
Cell Survival Curves
- Relationship between fraction of cells retaining reproductive integrity and absorbed dose of radiation
- Surviving fraction is plotted on logarithmic scale.
- Dose is on x-axis
- Slopes of survival curve represent radiosensitivity
- Steeper slope means more cell sensitivity
DNA Damage by Radiation
- Ionizing radiation can cause direct damage to DNA.
- Indirect damage is caused by free radicals and reactive oxygen species
Characteristics of Cell Survival Curves
- Slope is a measure of radiosensitivity. Steeper slope indicates more radiosensitivity.
Survival Curve Shoulder
- Represents the transition from single-hit to multiple-hit cell killing.
- Represents the repair capability of the cell population
- Shoulder is wider for slowly dividing cells
- Shoulder is narrower for rapidly dividing cells
Mammalian Cell Survival Curve
- Not exponential in low doses of radiation
- Exponential in high doses of radiation
- Turns flat at higher doses.
Factors Affecting Survival Curve
- Linear Energy Transfer (LET)
- Oxygen (Oxygen Enhancement Ratio (OER))
- Cell cycle
LET and Effect on Survival
- LET is Linear Energy Transfer, measured in keV/micron.
- High LET radiation increases killing per unit of energy.
- High LET radiation creates severe repair deficiencies and removes the repair shoulder effectively.
- High LET radiation is densely ionizing and averages >1 ionization event within a span of a DNA molecule.
- High ionization density increases probability of double strand breaks.
- Maximum effect of high LET is at about 100 keV/micron
- Photons have an average LET of about 1, <1 ionization event within the diameter of a DNA molecule, single strand breaks predominate, repair is permitted.
OER
- Oxygen Enhancement Ratio (OER) is the ratio of doses under hypoxic and aerated conditions that produce same biological effect.
- Presence of molecular oxygen dramatically influences the effects of radiation on cells.
- Presence of oxygen increases radiation effectiveness (killing of cells).
- Lack of oxygen (Hypoxic cells) results in more radioresistant cells.
Cell Cycle and Radiation Sensitivity
- Mitosis is the most sensitive phase of the cell cycle.
- G2 phase is similarly sensitive.
- S phase is the most radioresistant in the cell cycle.
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Description
Test your knowledge on radiation damage to DNA, cell survival curves, and factors affecting cell survival. This quiz also covers acute radiation syndrome and the mechanisms of DNA repair. Prepare to assess your understanding of essential concepts in Radiation Biology.
