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Principles of radiobiology — DNA damage, oxygen and fractionation
Radiation kills cells mainly through DNA double-strand breaks, most of them formed indirectly by free radicals from water; splitting the dose into small fractions exploits differences between normal tissue and tumour in repair, reoxygenation, cell-cycle redistribution and repopulation.
Why it matters in the exam
Every year the bank includes several short radiobiology questions: the main damage mechanism of photon radiation, how heavy-particle radiation differs, what happens to tumour cells between fractions, which mechanism normal cells use to repair double-strand breaks, and which radiation is preferred in a hypoxic tumour. These are factual questions where points are earned quickly.
Questions also link biology to the clinic: why loss of a homologous recombination gene increases sensitivity to radiation and PARP inhibitors, how drugs such as paclitaxel, cisplatin and temozolomide increase radiosensitivity, and which fractionation is chosen when combining radiation with immunotherapy. The LQ model and the α/β ratio explain why the prostate and late-responding tissues are sensitive to fraction size.
Key points
- The main lethal lesion is a DNA double-strand break, and with photons most of it is formed indirectly through free radicals from water.
- Oxygen fixes the damage, so hypoxic cells are more resistant; high-LET radiation is less oxygen-dependent.
- NHEJ is the main repair mechanism in normal cells, and loss of homologous recombination increases sensitivity to radiation and PARP inhibitors.
- The five Rs — repair, reoxygenation, redistribution, repopulation and intrinsic radiosensitivity — are the basis of fractionation.
- A low α/β ratio (late tissues and prostate) means high sensitivity to fraction size, which is the logic of hypofractionation in the prostate.
Summary table
| Concept | Key points | Clinical meaning |
|---|---|---|
| Indirect versus direct action | With photons about two thirds of the damage is indirect, through hydroxyl radicals from water | With heavy particles (high LET) damage is direct, dense and less oxygen-dependent |
| Oxygen effect | Oxygen "fixes" the damage and prevents its repair; hypoxic cells are 2.5 to 3 times more resistant | Hypoxic tumour — advantage for high-LET radiation, and importance of reoxygenation between fractions |
| Double-strand break repair | NHEJ — the main mechanism in normal cells, in all cycle phases and mainly in G1; homologous recombination in S and G2 | Loss of BRCA or other homologous recombination genes increases sensitivity to radiation, platinum and PARP inhibitors |
| The five Rs | Repair, reoxygenation, redistribution in the cell cycle, repopulation, intrinsic radiosensitivity | These occur between fractions and are the biological basis of fractionation |
| Cell-cycle sensitivity | Most sensitive in G2 and mitosis, most resistant in late S phase | Taxanes arrest cells in G2/M and so increase radiosensitivity |
| LQ model and α/β ratio | Tumours and early-responding tissues — about 10 Gy; late-responding tissues — about 3 Gy; prostate — about 1.5 Gy | A low ratio means high sensitivity to fraction size — hence hypofractionation in the prostate |
| Radiation and immunotherapy | Moderate-high fractions such as 8 Gy in 3 fractions promote an immune response | A very high single dose activates an enzyme that degrades cytoplasmic DNA and weakens the immune signal |
A free exam question
( קיטוע Fractionation ) בטיפול קרינתי מבוסס על תכונות רדיוביולוגיות המכונות ארבעת ה- R’s ?. מה מבין הבאים משפיע על תכונות רדיוביולוגיות אלה (the question as examined, in Hebrew)
- א. Re-Oxygenation מושפע משיעור האנטי - ( אוקסידנטים Anti-Oxidants ) .ברקמה הגידולית
- ב. Repopulation, Reassortment, Repair תלויים בזמן בין מקטעי הקרינה
- ג. Relative Biologic Effectiveness (RBE) .הוא מדד של תלות תאי הגידול בגודל הפרקציות
- ד. השפעת הקרינה בשיטת SBRT מבוססת בעיקר על Repair .של הנזק הקרינתי לרקמה הבריאה
In the full version for subscribers
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Sources
- Hall and Giaccia, Radiobiology for the Radiologist, 8th ed. (2018) — DNA strand breaks and chromosomal aberrations; Repair of radiation damage and the dose-rate effect; Oxygen effect and reoxygenation
- Joiner and van der Kogel, Basic Clinical Radiobiology, 5th ed. (2018) — The linear-quadratic approach; Fractionation
Sources are given for further reading; the text is written afresh and not copied from them.
Reviewed by the Examqo AI Professor · 2026-11-06. The text may contain errors; when in doubt, check the source.