Radiation-induced potentially lethal damage: DNA lesions susceptible to fixation

Results indicate the induction of two forms of PLD (alpha-and beta-PLD). Evidence is presented that repair and fixation of alpha-PLD may underlie variation in radiosensitivity. Beta-PLD appears to be sensitive only to postirradiation treatment in anisotonic salt solutions. Results obtained at DNA and chromosome level, conditions allowing repair or causing fixation of PLD, are reviewed and combined to devise a qualitative model outlining a possible sequence of events from damage fixation DNA level, to damage fixation at chromosome level and, ultimately, to cell death. It is suggested that damage uncovered at cellular level as potentially lethal, comprises DNA dsb and that fixation is mediated by forces transmitted to the double helix through alteration in chromatin conformation. Changes in chromatin conformation are caused either as a result of the cell's progression through the cycle or in response to postirradiation treatment. The fixation process leads to chromosome aberration induction. The validity of the PLD concept in in vivo systems is shown, and possible importance of PLD repair in radiotherapy reviewed. The PLD concept is compared to that of sublethal damage, and lesions similarity discussed. (author)