DNA Strand Break Induction and Rejoining and Cellular Recovery in Mammalian Cells after Heavy-Ion Irradiation

Abstract

The induction of intracellular DNA strand breaks by X rays and various heavy charged particles was measured by the alkaline unwinding and alkaline and neutral filter elution techniques. No variations in strand break induction were found between the different cell lines under investigation. For a given particle, both the LET and the particle energy determined the efficiency to induce DNA lesions. RBE values for the total amount of induced strand breaks were always less than 1. For DNA double-strand breaks (DSBs), RBE values only slightly greater than 1 were determined for particle radiation with an LET around 300 keV/microns. Intracellular DSB/SSB ratios were found to be equivalent to data reported for in vitro systems using radioprotective conditions [Christensen et al., Int. J. Radiat. Biol. 22, 457-477, 1972; Taucher-Scholz et al., Adv. Space Res. 12(2-3), (2)73-(2)80, 1992]. Strand break rejoining as an indicator of cellular repair processes was detected even after high-LET irradiation (LET < or = 10,000 keV/microns). However, both the half-times of rejoining and the fraction of residual DNA breaks increased with the atomic number of the particle. After particle irradiation with LET values beyond 10,000 keV/microns, no rejoining of DNA strand breaks was found.

Double Strand Breaks Induced by Low Doses of γ Rays or Heavy Ions: Quantitation in Nonradioactive Human DNA

“…This obscures the true extent comparable energy and linear energy transfer value (18,20,29). Our data clearly indicate higher yields of of the ''tail'' of DNAs at the small molecular length edge of the 1.3-Mbp group, producing an underestimate of DSBs per dose induced by Fe 26/ than by g rays, more in agreement with the data of Kampf (20), who used the number of these small molecules in the group.…”

“…This results in an overestimate of the number average mo-sucrose gradient sedimentation to measure DSB frequencies, than with those of Lobrich et al, who mealecular length, and thus an underestimate of the frequency of double strand breaks. Thus, we limit the sured depletion of a radioactively probed NotI cleavage population on CHEF gels (29), or of Heilmann et al, range of the current assay, for human DNA cleaved with NotI and electrophoresed using this TAFE regime, who used neutral elution (18). to Ç30 DSB/Gbp.…”

“…Unir-trinsic factors (5,6,13,18,22, 33,50). the well compared to that in the gel are more likely to affect fluorescent labels than radiolabels, many investigators limit this method to radiolabeled DNA.…”

The biological effects induced by high-charged and energy particles and its application in cancer therapy

“…The studies showed that clustered DSBs lesions induced by Fe particles are dif2icult to be repaired and resulting in elevated chromosome instability and enhanced cellular radiosensitivity (40,41) . The dif2iculty of repairing the clustered DSBs may due to the nature of the complex DNA damage induced by dense ionizations along the HZE particle track (19,22,(42)(43)(44)(45) . In mammalian cells, DNA DSBs are repaired mainly by two distinct pathways: nonhomologous end joining (NHEJ) and homologous recombination (HR).…”

Limited Repair of Critical DNA Damage in Cells Exposed to Low Dose Radiation

“…There is literature evidence that DSB repair in cells irradiated with high-LET IR is less efficient than in the case of low-LET radiation. This is due, exclusively, to the complexity of these breaks (Heilmann et al, 1993;Dianov et al, 2001). Tandems of different single lesions with DSB may further complicate the repair of both types of injury and increase their biological significance (Sutherland et al, 2000;Sage and Harrison, 2011).…”