RADIOBIOLOGY:
PRINCIPLES, MODELS,
AND THERAPEUTIC
APPLICATIONS
[Document subtitle]
,1. Introduction and Scope of Radiobiology
Definition & Purpose: Radiobiology is the study of the interactions between
ionizing radiation and living systems (cells, tissues, organisms), including how
radiation causes damage at molecular, cellular and tissue/organism levels — and
the consequences such as cell death, mutation, cancer, tissue dysfunction, or
therapeutic effects.
Applications: Understanding radiation effects is crucial for radiation protection,
radiological safety, cancer radiotherapy, medical diagnostics (radiology),
environmental radiation exposure, and radiogenetics (heritable effects).
Historical/Conceptual Foundation: Key radiobiological models link physical
radiation interactions → molecular damage (especially DNA) → cellular effects
(death, mutation, repair) → tissue/organ/organism outcomes (acute damage,
long-term carcinogenesis, etc.).
2. Physics of Radiation & Quality: Types of Radiation, LET, Dose
Definitions
To understand biological effects, one must appreciate the physical nature of radiation
and how its physical characteristics modulate biological damage.
Ionizing vs Non-Ionizing Radiation: Radiobiology mostly deals with ionizing
radiation — radiation with enough energy to remove (ionize) electrons from
atoms or molecules, thereby creating charged ions. This ionization is what can
damage critical biomolecules like DNA.
Linear Energy Transfer (LET): A critical parameter defining radiation quality.
LET refers to the energy deposited by radiation per unit track length (commonly
keV/µm).
o Low-LET radiation (e.g. X-rays, γ-rays) deposits energy sparsely along its
path — tends to cause indirect damage via intermediates (free radicals
formed by water radiolysis).
o High-LET radiation (e.g. α-particles, heavy ions, neutrons) deposits energy
densely — more likely to cause direct ionizations in DNA or other critical
macromolecules, leading to severe, often irreparable damage.
Dose and Dose Rate:
o Dose (e.g. Gray, Gy) measures energy absorbed per mass; biological
consequences often depend on total absorbed dose.
, o Dose rate (how fast dose is delivered) influences damage and repair: high
dose rates may overwhelm repair mechanisms; low dose rates may allow
repair to occur between events.
Relative Biological Effectiveness (RBE): Because different types of radiation
cause different damage per energy deposited (due to LET differences), the
biological effect per Gray may vary. High-LET radiation has greater RBE
compared to low-LET radiation.
3. Mechanisms of Radiation Damage: Molecular and Cellular
Levels
3.1 Direct vs Indirect Action
Radiation can damage cells via two main routes: direct action, and indirect action.
Direct Action: Radiation deposits energy directly into critical cellular
macromolecules (especially DNA), causing ionization or excitation and breaking
chemical bonds in the DNA backbone or base moieties. This can cause single-
strand breaks (SSBs), double-strand breaks (DSBs), base damage, crosslinks
(DNA–protein), etc.
Indirect Action: Much of the cell is water. Radiation interacts with water
molecules to produce free radicals (e.g. hydroxyl radicals OH • , hydrogen radicals
H • , ions), reactive oxygen species (ROS) that diffuse and react with DNA,
proteins, lipids, etc., causing oxidative damage.
o Radiolysis of water: radiation splits water → creates free radicals and ions
→ radicals interact with biomolecules → damage ensues.
3.2 Types of Molecular Damage
Depending on the interaction mechanism and radiation quality/dose, various molecular
lesions can arise:
Base damage (oxidized bases, deamination)
Single-strand breaks (SSBs)
Double-strand breaks (DSBs) — more dangerous, because both strands are
broken and repair is more challenging.
Cross-links (DNA–DNA, DNA–protein, protein–protein)
Complex clustered damage (multiple lesions in close proximity) — especially
problematic for repair.
PRINCIPLES, MODELS,
AND THERAPEUTIC
APPLICATIONS
[Document subtitle]
,1. Introduction and Scope of Radiobiology
Definition & Purpose: Radiobiology is the study of the interactions between
ionizing radiation and living systems (cells, tissues, organisms), including how
radiation causes damage at molecular, cellular and tissue/organism levels — and
the consequences such as cell death, mutation, cancer, tissue dysfunction, or
therapeutic effects.
Applications: Understanding radiation effects is crucial for radiation protection,
radiological safety, cancer radiotherapy, medical diagnostics (radiology),
environmental radiation exposure, and radiogenetics (heritable effects).
Historical/Conceptual Foundation: Key radiobiological models link physical
radiation interactions → molecular damage (especially DNA) → cellular effects
(death, mutation, repair) → tissue/organ/organism outcomes (acute damage,
long-term carcinogenesis, etc.).
2. Physics of Radiation & Quality: Types of Radiation, LET, Dose
Definitions
To understand biological effects, one must appreciate the physical nature of radiation
and how its physical characteristics modulate biological damage.
Ionizing vs Non-Ionizing Radiation: Radiobiology mostly deals with ionizing
radiation — radiation with enough energy to remove (ionize) electrons from
atoms or molecules, thereby creating charged ions. This ionization is what can
damage critical biomolecules like DNA.
Linear Energy Transfer (LET): A critical parameter defining radiation quality.
LET refers to the energy deposited by radiation per unit track length (commonly
keV/µm).
o Low-LET radiation (e.g. X-rays, γ-rays) deposits energy sparsely along its
path — tends to cause indirect damage via intermediates (free radicals
formed by water radiolysis).
o High-LET radiation (e.g. α-particles, heavy ions, neutrons) deposits energy
densely — more likely to cause direct ionizations in DNA or other critical
macromolecules, leading to severe, often irreparable damage.
Dose and Dose Rate:
o Dose (e.g. Gray, Gy) measures energy absorbed per mass; biological
consequences often depend on total absorbed dose.
, o Dose rate (how fast dose is delivered) influences damage and repair: high
dose rates may overwhelm repair mechanisms; low dose rates may allow
repair to occur between events.
Relative Biological Effectiveness (RBE): Because different types of radiation
cause different damage per energy deposited (due to LET differences), the
biological effect per Gray may vary. High-LET radiation has greater RBE
compared to low-LET radiation.
3. Mechanisms of Radiation Damage: Molecular and Cellular
Levels
3.1 Direct vs Indirect Action
Radiation can damage cells via two main routes: direct action, and indirect action.
Direct Action: Radiation deposits energy directly into critical cellular
macromolecules (especially DNA), causing ionization or excitation and breaking
chemical bonds in the DNA backbone or base moieties. This can cause single-
strand breaks (SSBs), double-strand breaks (DSBs), base damage, crosslinks
(DNA–protein), etc.
Indirect Action: Much of the cell is water. Radiation interacts with water
molecules to produce free radicals (e.g. hydroxyl radicals OH • , hydrogen radicals
H • , ions), reactive oxygen species (ROS) that diffuse and react with DNA,
proteins, lipids, etc., causing oxidative damage.
o Radiolysis of water: radiation splits water → creates free radicals and ions
→ radicals interact with biomolecules → damage ensues.
3.2 Types of Molecular Damage
Depending on the interaction mechanism and radiation quality/dose, various molecular
lesions can arise:
Base damage (oxidized bases, deamination)
Single-strand breaks (SSBs)
Double-strand breaks (DSBs) — more dangerous, because both strands are
broken and repair is more challenging.
Cross-links (DNA–DNA, DNA–protein, protein–protein)
Complex clustered damage (multiple lesions in close proximity) — especially
problematic for repair.
