General aspects of the cellular response to low- and high-LET radiation

Radiobiological studies have shown for some time that the effects of ionisi ng radiation on cells are mainly explained by modification of the DNA. Nume rous studies over the past 50 years have accumulated clear evidence of the cause-effect relationship between damage to DNA and the cytotoxic and mutag enic effects of ionising radiation. However, the path from irradiation of t he cells to the induction of biological effects comprises several complex s teps. The first step involves interactions between the radiation and the ce llular environment. These consist of physical and chemical reactions which produce ions, excited molecules and radical species. Excitations and ionisa tions are complete in about 10(-15) s, and are followed by a chemical therm al equilibrium of the species produced within 10(-12) s. These species then diffuse from their site of production and provoke alterations to a variety of cellular components. This damage is detected by cellular surveillance s ystems, which in turn activate signalling cascades, gene transcription and enzyme recruitment, which participate in the cellular response. In most cas es, cell cycle arrest occurs, allowing, according to the biological relevan ce of the DNA damage, either a process of DNA repair or programmed cell dea th (apoptosis). The accuracy of the DNA repair which is performed depends o n the complexity of the DNA lesion and on the DNA repair machinery fidelity itself. Improper DNA repair can lead to mutation, chromosome aberration, g enetic instability, oncogenic transformation and, ultimately, cell death.