Biological basis of radiation sensitivity Part 2: Cellular and molecular determinants of radiosensitivity

Recent studies have elucidated some of the molecular and cellular mechanism s that determine the sensitivity or resistance to ionizing radiation, These findings ultimately may be useful in devising new strategies to improve th e therapeutic ratio in cancer treatment. Despite the rapid advances in know ledge of cellular functions that affect radiosensitivity, we still cannot a ccount for most of the clinically observed heterogeneity of normal tissue a nd tumor responses to radiotherapy, nor can we accurately predict which ind ividual tumors will be controlled locally and which patients will develop m ore severe normal tissue damage after radiotherapy, However, several candid ate genes for which deletion or loss of function mutations may be associate d with altered cellular radiosensitivity leg, ATM, p53, BRCA1, BRCA2, DNA-P K) have been identified. Some of the differences in normal tissue sensitivi ty to radiation may stem from mutations with milder effects, heterozygosity , or polymorphisms of these genes. Finally, molecular mechanisms linking ge netic instability, radiosensitivity, and predisposition to cancer are being unraveled.