Radiobiology: Cellular Response to Radiation
1. Introduction to Radiobiology
Radiobiology is the study of how radiation interacts with living cells and tissues, particularly the effects of ionizing radiation on biological systems. Understanding cellular responses to radiation is essential for radiation therapy, radiation protection, and medical imaging.
2. Cellular Response to Radiation
When a cell is exposed to ionizing radiation, several possible outcomes can occur:
- Cell Death (Apoptosis or Necrosis) – The cell loses function and dies.
- Cellular Repair – The cell repairs the radiation-induced damage.
- Mutation and Malignancy – The cell survives but with mutations, potentially leading to cancer.
- Mitotic Delay – The cell cycle is temporarily halted to repair damage before division.
3. Cell Survival Curves
A cell survival curve represents the fraction of cells that remain alive after different doses of radiation. It is semi-logarithmic, with:
- X-axis: Radiation dose (Gy).
- Y-axis: Surviving fraction of cells (log scale).
3.1 Key Parameters of the Cell Survival Curve
- D₀ (Mean Lethal Dose): The dose required to reduce survival to 37%.
- Dq (Quasi-threshold Dose): The dose below which significant cell death does not occur.
- n (Extrapolation Number): Indicates the cell’s ability to repair damage.
- α/β Ratio: Determines tissue sensitivity in the linear-quadratic model used in radiotherapy.
3.2 Multi-Hit Target Theory
- Single-Hit, Single-Target Model: Used for simple cells (e.g., bacteria).
- Multi-Hit, Multi-Target Model: Used for mammalian cells, which can survive low doses due to DNA repair mechanisms.
4. Fractionation in Radiation Therapy
Fractionation refers to delivering radiation in multiple small doses rather than a single large dose. It allows:
- Normal tissue repair between doses.
- Increased tumor kill efficiency due to reoxygenation and reassortment.
4.1 Types of Fractionation
- Conventional Fractionation: 1.8–2.0 Gy per fraction, once daily, over weeks.
- Hyperfractionation: Smaller doses (e.g., 1.2 Gy) given twice daily to reduce late toxicity.
- Hypofractionation: Larger doses (e.g., 3–7 Gy) in fewer sessions, used in stereotactic radiotherapy.
5. The Four Rs of Radiobiology
The effectiveness of fractionation is explained by the Four Rs of Radiobiology:
5.1 Repair
- Normal cells can repair sublethal damage better than cancer cells.
- A delay between doses allows healthy tissue to recover.
5.2 Reoxygenation
- Tumors often have hypoxic (low oxygen) regions that resist radiation.
- Fractionation allows time for tumor reoxygenation, making remaining cells more radiosensitive.
5.3 Redistribution (Reassortment)
- Cells in different cell cycle phases have different radiosensitivity.
- Fractionation redistributes surviving cells, exposing them at more sensitive phases.
5.4 Repopulation
- Normal tissues regenerate between radiation fractions.
- Tumor repopulation occurs, but at a slower rate, allowing effective cancer control.
6. Radiation Sensitivity and Cell Cycle Dependence
Cells are more sensitive to radiation in specific phases of the cell cycle:
- Most Sensitive: G2 and M (mitosis) phases.
- Moderately Sensitive: G1 phase.
- Least Sensitive: S phase (active DNA repair).
7. Conclusion
- Cell survival curves describe how cells respond to different radiation doses.
- Fractionation is crucial in radiotherapy to maximize tumor control while minimizing normal tissue damage.
- The Four Rs (Repair, Reoxygenation, Redistribution, and Repopulation) explain why fractionation improves treatment effectiveness.
