RADS 335 Lecture 2 notes (1)

Lecture Overview

  • Focuses on fundamental principles of radiobiology

  • Examines radiation damage to cells and factors affecting radiosensitivity

Radiation Damage to Cells

  • Radiation undoubtedly causes harmful biological effects

  • All ionizing radiation types induce similar damage

  • Alpha particles are more potent than x-rays or gamma radiation

  • Damages impact essential cellular molecules through:

    • Excitation of an orbital electron

    • Ionization of the atom

  • Interaction is random with visible damage indistinguishable from other trauma

Possible Cell Interactions with Radiation

  1. Pass through without damage

  2. Damage but full recovery occurs

  3. Damage with partial recovery; may slow cell mitosis

  4. Damage causes generational defects

  5. Sterilization or cell death

Reversibility of Radiation Damage

  • Processes can reverse:

    • Ionized atoms can neutralize by attracting free electrons

    • Excited electrons can release excess energy

    • Enzymatic repairs can fix damaged molecules

    • Cells and tissues can regenerate and recover

  • Incomplete repairs can lead to long-term effects:

    • Cancer

    • Genetic mutations

    • Birth defects

Law of Bergonie and Tribondeau

  • Developed by Bergonie and Tribondeau in 1906, addressing radiosensitivity

  • Key points:

    • Stem cells are more radiosensitive than mature cells

    • Younger tissues and organs display increased sensitivity

    • High metabolic activity increases radiosensitivity

    • High cell proliferation rate correlates with higher sensitivity

Factors Affecting Radiosensitivity

General Factors

  • Relative susceptibility of cells, tissues, and organs to ionizing radiation

  • Identical doses may yield varied responses due to:

    • Physical factors

    • Biological factors

Physical Factors

  • Linear Energy Transfer (LET): Rate of energy transfer from radiation to tissue (measured in keV/μm)

    • Diagnostic x-rays ~3 keV/μm

    • 5MeV alpha particles ~100 keV/μm

  • Relative Biological Effectiveness (RBE): Measures biological effectiveness of radiation with differing LETs

    • Higher LET generally leads to more biological damage

    • RBE = Dose of reference radiation / Dose of test radiation

    • Standard reference is 200-250 kVp x-rays, where RBE = 1

Protraction and Fractionation

  • Protraction: Continuous dose delivery at reduced rate

  • Fractionation: Divided doses at regular intervals

  • Both methods allow for cellular repair and recovery

Biological Factors

  • Oxygen Effect: Increased radiosensitivity in oxygenated tissues compared to anoxic conditions

    • Described with Oxygen Enhancement Ratio (OER)

    • OER highest for low LET radiation (3) and 1 for high LET radiation

  • Age: Sensitivity varies with age, highest at birth and again in old age

  • Recovery: Cells may recover from sublethal damage via repair mechanisms or repopulation

  • Chemical Agents: Modify radiosensitivity

    • Radiosensitizers enhance radiation effects (e.g., halogenated pyrimidines)

    • Radioprotectors reduce effects (e.g., sulfhydryl groups)

  • Hormesis: Low radiation doses may produce beneficial effects, controversial and debated

Dose-Response Relationships

Linear Nonthreshold

  • No safe level of radiation; response is directly proportional to radiation received

Linear Threshold

  • Response begins only after a certain dose, then increases proportionally

Nonlinear Nonthreshold

  • No safe level; response grows but not in direct proportion to the dose

Nonlinear Threshold

  • Response begins only above a certain threshold, not in proportional relation

S-type or Sigmoid Type

  • Responding increases until an inflection point; beyond which, increased doses yield less response

Stochastic vs. Deterministic Effects

Deterministic Effects

  • Results from high-dose exposure (immediate response), affected function if sufficient cells die


    • Dose-Response: linear threshold, nonlinear threshold, sigmoid

    • Includes effects like skin damage, cataracts

Stochastic Effects

  • Occur with low-dose exposure; probability increases without a dose threshold

    • Severity is independent of the dose

    • Associated with cancer, leukemia, genetic effects

    • Latency period varies significantly: years for cancer, hundreds for hereditary effects

Summary of Effects

  • Deterministic: Early effects (nausea, hair loss) tied to high doses

  • Stochastic: Late effects (cancer, genetic effects), tied to low doses, with no threshold for occurrence.