ABSTRACT
The effects of radiation on human tissues involve a succession of processes extending from microseconds after exposure, to months and years thereafter. DNA is the most important target for radiation. A therapeutic dose of radiation produces in every exposed cell fast electrons and a large number of ionizations. Some of these directly damage DNA, others indirectly damage DNA by generating free radicals (in an oxygen dependant reaction) that react with DNA. Chemical lesions in DNA are very effectively repaired, but some of them fail to repair and oxygen acts to fix free radical damage. On average, for every cell killed by radiation, there may be more than 1000 damaged bases, 1000 single-strand breaks, and 40 doublestrand DNA breaks. This DNA damage, if not repaired, leads to cell death rapidly or after several cell divisions. Therefore, cells with a short mitotic cycle will show signs of radiation damage more quickly. Clinical radiotherapy has been found to be most effective if administered in multiple fractions. This is thought to be due to a number of processes. The five Rs of radiobiology underlying this are:
Radiosensitivity (cellular) • Repair (of DNA damage) • Reassortment (of cell cycle distribution) • Repopulation (of surviving cells) • Reoxygenation (of hypoxic tissue) •
An intriguing range of radiation sensitivity is seen in different types of tumor. For example, with conventionally fractionated radiotherapy a dose of about 25 gray (Gy) is needed to control a 2 cm seminoma, a dose of 35-40 Gy to control a 2 cm lymphoma, and upwards of 60 Gy to control a similar size of epithelial tumor, such as squamous carcinoma of the head and neck. Doses over 70 Gy will not control a small high-grade astrocytoma. A similar range of radiosensitivity is seen in the laboratory in cell lines derived from these human tumors. The biological basis of this intrinsic cellular radiosensitivity remains imperfectly understood (1). Overlaid on these differences, evidence has developed that variations or polymorphisms in key DNA repair pathways can affect both host and tumor radiosensitivity. This is most clearly shown in a number of rare radiotherapy sensitivity syndromes with recognized major defects
Radiation has been used in the management of cancer for the last 100 years. It is estimated to be used in about half of patients who develop cancer in the United Kingdom each year, with a curative role in approximately two-thirds of these and a palliative role in the remainder ( Table 5.1 ).
