The genetic basis of cellular recovery from radiation damage: response of the radiosensitive irs lines to low-dose-rate irradiation.

Recovery from the lethal effects of irradiation is commonly found when cultured mammalian cells are irradiated at low dose rates when compared to the same cells irradiated at higher dose rates. However, this cellular recovery process is severely reduced or absent in a number of radiosensitive cell lines, including those derived from the human disorder ataxia telangiectasia (AT). The genetic and molecular basis of such recovery processes is not understood, despite their importance. The responses of cells of three further radiosensitive lines, irs1, irs2 and irs3, shown previously to be mutated in different genes, to low-dose-rate radiation are now presented. Plateau-phase cultures of cells of the irs2 line were found to have little or no cellular recovery, while irs1 and irs3 had considerable recovery potential. In comparing the known properties of the radiosensitive lines lacking cellular recovery, including xrs, XR-1 and scid as well as AT and irs2, it is argued that the gene products lacking in these lines normally act coordinately in a specific damage-recognition pathway. The recovery pathway is likely to be associated with the rejoining of DNA double-strand breaks, since several of these recovery-defective lines have a measurable deficiency in break repair.