Do Low Doses of Radiation Induce a Response Modulating Induction or Repair of DNA Single-Strand Breaks?

Many recent reports have indicated interesting structure in the low-dose region of survival curves for mammalian cells (e.g., variations in the effects of oxygen, high-order modulation of the dose-response function, induction of repair, activation of protein-modifying enzymes, influences of cytokines, etc.). Since we have recently identified and corrected several problems causing variability in the results of the alkaline elution methodology, we felt that it was important to investigate the formation and repair of single-strand breaks (SSBs) in this low-dose region. To date we have asked three questions relevant to the structure features noted above: (1) Is the dose response linear at very low radiation doses? (2) Is repair of SSBs complete? (3) Do low "priming" doses of radiation induce subsequent variations in the sensitivity, or rate or extent of repair? To date, we have found no basis in SSB induction and repair for the interesting substructure noted in the survival responses above. At doses from 0.25 Gy to 4 Gy in air, no significant deviations from a linear dose response were observed, and a "priming" dose of 2 Gy has a minimal effect on subsequent sensitivity of SSB formation. Repair of SSBs appears complete at clinical doses of 2 Gy, but substantial unrepaired SSB damage remains 1 h after doses (11 Gy) corresponding to a surviving fraction of 0.01. No significant change in repair of SSBs at 4 h after a 2-Gy priming dose has yet been determined.