Irradiation of Macromolecules Quiz

Exposure

• In Vitro irradiation (outside the body) of macromolecules requires a significant radiation dose to produce measurable effects.
• In Vivo irradiation (inside the body) shows macromolecules are more radiosensitive in their natural state.

Irradiation of Macromolecules

• Solutions are liquids containing dissolved substances, including mixtures like water and alcohol.
• Irradiation of macromolecules in solution (in vitro) can cause three main effects:
  • Main-chain scission: Breaking the backbone of long chain macromolecules into smaller molecules, reducing solution viscosity.
  • Cross-linking: Formation of spur-like molecules extending from the main chain, increasing solution viscosity.
  • Point lesions: Disruption of single chemical bonds, causing minor modifications and potential malfunction within the cell.
• Stochastic radiation effects can be observed at the whole-body level.
• These effects are usually reversible through intracellular repair processes.

Radiolysis of Water

• Irradiation of water causes ionization and dissociation into H2O+ and free electrons.
• Ion pairs may rejoin without damage, or the free electron can create additional ions (e.g., HOH-).
• Dissociation of HOH+ and HOH- ions can produce hydroxyl and hydrogen radicals (highly reactive).
• Hydroxyl radicals can combine to form hydrogen peroxide, a toxic agent to cells.

Radiation Response of DNA

• DNA is complexed with other molecules within chromosomes.
• Radiation can cause various types of damage to DNA, including:
  • Main-chain scission (single or double strand breaks)
  • Cross-linking
  • Rung breakage
  • Base changes
• Repeated cell recovery and proliferation can lead to metabolic dysfunction and uncontrolled cell proliferation (cancer).

Macromolecular Synthesis

• Anabolism involves building larger molecules from smaller ones.
• Catabolism involves breaking down larger molecules into smaller ones.

Target Theory

• Cell death occurs when a crucial target molecule (e.g., DNA) is inactivated.
• Interactions between radiation and the target are called Hits.

Direct and Indirect Effects

• Direct effects occur when radiation interacts directly with the target molecule (DNA), often leading to cell death.
• Indirect effects involve radiation interacting with water molecules, forming free radicals that damage other cellular components, potentially avoiding direct cell death.

Cell Survival Kinetics

• Single-target, single-hit models apply to simple biological targets like enzymes, viruses, and bacteria.
• Multi-target, single-hit models apply to more complex systems like human cells.
  • Both models use values like D37 (dose where 37% of cells survive) and extrapolation number (n) to quantify cell radiosensitivity.
• Cell radiosensitivity can be measured using these models as well regarding the effect of various radiation types and doses on the relative cell survival.

Extrapolation Number

• A measure of the shoulder width in cell survival curves.
• Larger values suggest greater capacity for cell recovery from sublethal damage.

Oxygen Enhancement Ratio (OER)

• A measure of the effect of oxygen on radiation sensitivity.
• Oxygen presence maximizes low-LET radiation effects and increases a need for a higher dose to achieve the same effect in Anoxic cells.