The Severity of Alpha-Particle-Induced DNA Damage Is Revealed by Exposure to Cell-Free Extracts

The rejoining of single-strand breaks induced by α-particle and γ irradiation in plasmid DNA under two scavenging conditions has been compared. At the two scavenger capacities used of 1.5× 10⁷ and|$3\times 10^{8}\ {\rm s}^{-1}$| using Tris-HCl as the scavenger, the ratio of single- to double-strand breaks for α particles is fivefold less than the corresponding ratios for γ irradiation. The repair of such radiation-induced single-strand breaks has been examined using a cell-free system derived from human whole-cell extracts. We show that the rejoining of single-strand breaks for both α-particle- and γ-irradiated plasmid is dependent upon the scavenging capacity and that the efficiency of rejoining of α-particle-induced single-strand breaks is significantly less than that observed for γ-ray-induced breaks. In addition, for DNA that had been irradiated under conditions that mimic the cellular environment with respect to the radical scavenging capacity, 50% of α-particle-induced single-strand breaks are converted to double-strand breaks, in contrast with only ∼12% conversion of γ-ray-induced single-strand breaks, indicating that the initial damage caused by α particles is more severe. These studies provide experimental evidence for increased clustering of damage which may have important implications for the induction of cancer by low-level α-particle sources such as domestic radon.