Biological Effects of Ionising Radiation

Radiation transfers energy to atoms and molecules in cells. Ionisation and excitation can alter biological molecules, particularly DNA, leading to repair, cell death or lasting mutations.

Direct action occurs when radiation deposits energy in a critical molecule such as DNA, damaging it without an intermediate reactive species.

Indirect action occurs when radiation interacts with water and produces reactive chemical species that subsequently damage cellular molecules.

Ionising radiation can split or ionise water molecules, producing reactive species including hydroxyl radicals. These can damage DNA and other cell components.

Free radicals contain an unpaired electron and can be highly reactive. Hydroxyl radicals generated after irradiation are an important cause of indirect DNA damage.

A single-strand break damages one backbone of DNA. Cells can often repair these lesions, although misrepair may still occur.

A double-strand break affects both DNA strands and can be difficult to repair accurately. Unrepaired or incorrectly repaired breaks are important causes of radiation-induced cell death and mutation.

Cells use repair pathways to correct radiation-induced DNA damage. The outcome depends on lesion complexity, repair capacity and whether repair is accurate.

Radiation may cause apoptosis or other forms of cell death. A cell may also remain alive temporarily but lose its ability to divide successfully, called reproductive or clonogenic death.

Radiosensitivity describes how readily cells or tissues are damaged by radiation. Rapidly dividing, less differentiated cells are often more sensitive, although exceptions occur.

As a general principle, cells tend to be more radiosensitive when they divide frequently and are less differentiated. It is a useful rule of thumb, not an absolute law.

Tissues with rapid cell turnover may show effects during or soon after treatment, such as skin erythema or mucosal inflammation. Recovery depends on tissue and treatment conditions.

Late effects may develop months or years after exposure, including fibrosis or vascular damage. They may persist and are influenced by dose distribution and fraction size.

Tissue reactions, historically called deterministic effects, generally have a threshold dose; severity tends to increase as dose rises above that threshold. Examples include skin injury and cataract formation.

Stochastic effects are probabilistic outcomes such as radiation-induced cancer. For radiation protection, risk is generally assumed to increase with dose without a proven threshold, while severity is not determined by dose.

Absorbed dose is energy deposited per unit mass, measured in gray (Gy). Biological response also depends on radiation quality, dose rate, fractionation and tissue characteristics.

Fractionation divides a prescribed radiotherapy dose into separate treatment sessions. It can allow normal tissues time to repair some damage between fractions while maintaining tumour treatment.

The traditional four Rs are repair of sublethal damage, redistribution through the cell cycle, reoxygenation of hypoxic tumour cells and repopulation of surviving cells.

Normal and tumour cells can repair some radiation-induced injury between fractions. Differences in repair capacity help influence treatment response.

Cells vary in sensitivity across the cell cycle. Between fractions, surviving cells may move into different phases, altering their sensitivity at the next exposure.

Oxygen can enhance the effect of low-LET radiation. Some previously hypoxic tumour cells may become better oxygenated during a course of treatment.

Surviving cells may proliferate during treatment. Repopulation can aid normal-tissue recovery but can also reduce tumour control if treatment is prolonged.

Oxygen can make radiation-induced chemical damage harder to reverse, increasing the effectiveness of low-LET radiation. Hypoxic cells are often more radioresistant.

LET describes energy deposited per unit track length. Higher-LET radiation produces denser ionisation tracks and often more complex biological damage.

RBE compares doses of a test radiation and reference radiation required to produce the same biological effect. It depends on radiation type, dose and biological endpoint.

Radiotherapy aims to control tumour cells while limiting injury to normal tissues. Dose, fractionation, treatment volume and tissue sensitivity all matter.