Ionizing Radiation Damage to DNA

Abstract

At doses at which mammalian cells are killed, ionizing radiation produces 3 × 103 — 3 × 104 altered moieties in the genomic DNA of the cell. Mechanisms whereby these alterations are produced are well described, i.e., from ’OH radicals, direct ionization of DNA (von Sonntag, 1987) and perhaps from peroxyl radicals arising from ’OH reactions with other cellular molecules (Ward et al., 1997). Enzymatic repair of altered bases is well documented, and since these altered bases are produced during endogenous oxidation it is not surprising that enzymatic processes have evolved for their removal (Lindahl,1990). Ionizing radiation also produces strand breaks, but it is not known if these are produced by endogenous oxidation. The repair of singly damaged sites is well known. However, ionizing radiation also produces multiply damaged sites (MDS): It deposits energy non-uniformly; increments of energy (average amount 60eV) in small (nanometer) volumes. Thus a resulting radical reacting with DNA frequently does so in the presence of other radicals which can also react in close proximity. MDS have three variables: 1. Types of lesions involved (base damage, strand break); 2. Total number of lesions involved (for low LET radiation the most frequent is two); 3. Size of the site over which the damages are distributed. MDS represent a challenge to the cellular repair systems, they represent sites in the DNA at which base identity has been destroyed on both strands; if the damaged sites are closely opposed there is no complimentary strand to guide repair.