THE ROLE OF DNA SINGLE-STRAND AND DOUBLE-STRAND BREAKS IN CELL-KILLING BY IONIZING-RADIATION

Ionizing radiation produces many types of DNA lesions that have the po tential of killing cells. The lethal lesion is probably an unrepaired or misrepaired double-strand break produced as part of a complex lesio n. A variety of DNA damage assays have been applied in an effort to pr edict the sensitivity of cells to ionizing radiation. However, the rel ationships between initial DNA damage, rejoining of breaks and ultimat e cell killing by radiation are not fully understood or predictable. W hile most repair-deficient cell lines can be identified based on slowe r strand break rejoining, controversy surrounds the ability of DNA dam age assays to rank the radiosensitivity of tumor cells reliably in ter ms of results of clonogenic assays. Part of the difficulty may be that the most relevant lesions, those that are closely spaced locally or r egionally, cannot be easily quantified. It is also possible that the D NA damage can be interpreted differently (in relation to repairability ) depending on cell type and/or DNA damage assay. Repair itself does n ot always increase survival, and survival is the outcome of the action s of several pathways that can be both cell- and tissue-specific. Meas urements of misrepair leading to chromosome damage and mutation have b een helpful in ranking the radiosensitivity of cell lines, and may be a requirement for predictive assays. These concepts are illustrated wi th results from alkaline and neutral comet assays developed to detect single-strand breaks and double-strand breaks in individual cells. (C) 1998 by Radiation Research Society.