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 compar ed to the same cells irradiated at higher dose rates. However, this ce llular recovery process is severely reduced or absent in a number of r adiosensitive cell lines, including those derived from the human disor der ataxia telangiectasia (AT). The genetic and molecular basis of suc h recovery processes is not understood, despite their importance. The responses of cells of three further radiosensitive lines, irs1, irs2 a nd irs3, shown previously to be mutated in different genes, to low-dos e-rate radiation are now presented. Plateau-phase cultures of cells of the irs2 line were found to have little or no cellular recovery, whil e 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 th at the gene products lacking in these lines normally act coordinately in a specific damage-recognition pathway. The recovery pathway is like ly to be associated with the rejoining of DNA double-strand breaks, si nce several of these recovery-defective lines have a measurable defici ency in break repair. (C) 1995 by Radiation Research Society