Overview
This lecture provides a foundational overview of radiation biology, focusing on the nature of radiation, its cellular effects, DNA damage mechanisms, and the rationale behind fractionated radiation therapy.
What is Radiation?
- Radiation is energy that affects atoms at the atomic level, causing changes in electrons.
- Atoms have a nucleus (protons, neutrons) and orbiting electrons.
- Radiation can be ionizing (removes electrons) or non-ionizing (excites electrons without removal).
Types of Radiation
- Electromagnetic radiation includes photons (massless energy packets) like microwaves, visible light, X-rays, and gamma rays.
- X-rays and gamma rays are ionizing due to their high energy.
- Particulate radiation includes electrons (beta particles), protons, alpha particles, and neutrons—all are ionizing.
- Photons are commonly used in radiation therapy; electrons treat superficial lesions; protons have a defined stopping point sparing deeper tissues.
Direct vs. Indirect Ionization
- Charged particles (protons, electrons) are directly ionizing—they themselves cause ionization in tissue.
- Electromagnetic waves (X-rays, gamma rays) and neutrons are indirectly ionizing—they generate secondary particles (e.g., electrons) that cause ionization.
Atomic Interactions
- Photoelectric effect occurs at lower energies (diagnostic imaging); photons eject inner-shell electrons, and characteristic X-rays are released.
- Compton effect dominates at therapeutic energies; photons eject outer-shell electrons, producing ionized atoms and free electrons.
DNA Damage Mechanism
- Ionizing radiation leads to electron release, causing DNA damage mainly via direct and indirect actions.
- Direct action: electrons directly damage DNA.
- Indirect action (more common): electrons interact with water, generating free radicals that damage DNA.
- DNA damage can be single-stranded (repairable) or double-stranded (more lethal and less repairable).
Cell Cycle and Radiosensitivity
- Cells are most sensitive to radiation in the mitotic (M) phase.
- Cells are most resistant in the S and G2 phases due to enhanced DNA repair mechanisms.
Rationale for Fractionation
- Radiation doses are typically divided into multiple fractions to reduce toxicity and increase effectiveness.
- The Four R’s of radiobiology:
- Repair: Normal cells can repair damage between fractions; cancer cells are less efficient at repair.
- Repopulation: Allows normal tissue to recover; cancer cell repopulation is limited.
- Redistribution: Cells redistribute through the cell cycle, making more cells sensitive to subsequent doses.
- Re-oxygenation: Kills aerobic tumor cells first; surviving hypoxic cells become better oxygenated and thus more radiosensitive.
Modern Fractionation Techniques
- Hypofractionation and stereotactic radiation deliver higher doses in fewer sessions, enabled by precise targeting and advanced technology.
Key Terms & Definitions
- Ionizing Radiation — Radiation with enough energy to remove electrons from atoms, creating ions.
- Photon — A massless quantum of electromagnetic energy (e.g., X-ray, gamma ray).
- Photoelectric Effect — Ejection of an inner-shell electron by a photon, releasing a characteristic X-ray.
- Compton Effect — Scattering of a high-energy photon resulting in the ejection of an outer-shell electron.
- Direct Action — Radiation directly causes DNA damage.
- Indirect Action — DNA damage via intermediates like free radicals.
- Fractionation — Dividing the total radiation dose into smaller, multiple treatments.
- Four R’s — Principles explaining benefits of dose fractionation: repair, repopulation, redistribution, re-oxygenation.
Action Items / Next Steps
- Review the Four R’s of radiobiology for deeper understanding.
- Study cell cycle phases and their implications for radiosensitivity.
- Familiarize yourself with terms and differences between photon and particulate radiation.