MRD441: Radiation Biology & Safety Quiz

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.