General aspects of the cellular response to low- and high-LET radiation.
Radiobiological studies have shown for some time that the effects of ionising radiation on cells are mainly explained by modification of the DNA. Numerous studies over the past 50 years have accumulated clear evidence of the cause-effect relationship between damage to DNA and the cytotoxic and mutagenic effects of ionising radiation. However, the path from irradiation of the cells to the induction of biological effects comprises several complex steps. The first step involves interactions between the radiation and the cellular environment. These consist of physical and chemical reactions which produce ions, excited molecules and radical species. Excitations and ionisations are complete in about 10(-15) s, and are followed by a chemical thermal 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 systems, which in turn activate signalling cascades, gene transcription and enzyme recruitment, which participate in the cellular response. In most cases, cell cycle arrest occurs, allowing, according to the biological relevance of the DNA damage, either a process of DNA repair or programmed cell death (apoptosis). The accuracy of the DNA repair which is performed depends on the complexity of the DNA lesion and on the DNA repair machinery fidelity itself. Improper DNA repair can lead to mutation, chromosome aberration, genetic instability, oncogenic transformation and, ultimately, cell death.
Pouget
J P
JP
Nuclear Medicine Department, Imperial Cancer Research Fund, St Bartholomew's Hospital, London EC1A 7BE, UK.
Mather
S J
SJ
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D002453:Cell Cycle / Q000528:radiation effects*; D002477:Cells / Q000528:radiation effects*; D004260:DNA Repair / Q000528:radiation effects; D006801:Humans; D018499:Linear Energy Transfer / Q000528:radiation effects*