Cellular Radiosensitivity: How much better do we understand it?

Purpose: Ionizing radiation exposure gives rise to a variety of lesions in DNA that result in genetic instability and potentially tumorigenesis or cell death. Radiation extends its effects on DNA by direct interaction or by radiolysis of H2O that generates free radicals or aqueous electrons capable of interacting with and causing indirect damage to DNA. While the various lesions arising in DNA after radiation exposure can contribute to the mutagenising effects of this agent, the potentially most damaging lesion is the DNA double strand break (DSB) that contributes to genome instability and/or cell death. Thus in many cases failure to recognise and/or repair this lesion determines the radiosensitivity status of the cell. DNA repair mechanisms including homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to protect cells against DNA DSB. Mutations in proteins that constitute these repair pathways are characterised by radiosensitivity and genome instability. Defects in a number of these proteins also give rise to genetic disorders that feature not only genetic instability but also immunodeficiency, cancer predisposition, neurodegeneration and other pathologies. Conclusions: In the past fifty years our understanding of the cellular response to radiation damage has advanced enormously with insight being gained from a wide range of approaches extending from more basic early studies to the sophisticated approaches used today. In this review we discuss our current understanding of the impact of radiation on the cell and the organism gained from the array of past and present studies and attempt to provide an explanation for what it is that determines the response to radiation

Neurodevelopment of children exposed in utero to treatment of maternal malignancy

Cancer is the second most common cause of death during the reproductive years, complicating approximately 1/1000 pregnancies. The occurrence of cancer during gestation is likely to increase as a result of a woman's tendency to delay childbearing. Improved diagnostic techniques for malignancies increases detection of cancer during pregnancy. Malignant conditions during gestation are believed to be associated with an increase in poor perinatal and fetal outcomes that are often due to maternal treatment. Physicians should weigh the benefits of treatment against the risks of fetal exposure. To date, most reports have focused on morphologic observations made very close to the time of delivery with little data collected on children's long-term neurodevelopment following in utero exposure to malignancy and treatment. Because the brain differentiates throughout pregnancy and in early postnatal life, damage may occur even after first trimester exposure. The possible delayed effects of treatment on a child's neurological, intellectual and behavioural functioning have never been systematically evaluated. The goal of this report was to summarize all related issues into one review to facilitate both practitioners' and patients' access to known data on fetal risks and safety. © 2001 Cancer Research Campaign http://www.bjcancer.co