title: Spatial distribution and yield of DNA double-strand breaks induced by 3-7 MeV helium ions in human fibroblasts.
abstract: Accelerated helium ions with mean energies at the target location of 3-7 MeV were used to simulate alpha-particle radiation from radon daughters. The experimental setup and calibration procedure allowed determination of the helium-ion energy distribution and dose in the nuclei of irradiated cells. Using this system, the induction of DNA double-strand breaks and their spatial distributions along DNA were studied in irradiated human fibroblasts. It was found that the apparent number of double-strand breaks as measured by a standard pulsed-field gel assay (FAR assay) decreased with increasing LET in the range 67-120 keV/microm (corresponding to the energy of 7-3 MeV). On the other hand, the generation of small and intermediate-size DNA fragments (0.1-100 kbp) increased with LET, indicating an increased intratrack long-range clustering of breaks. The fragment size distribution was measured in several size classes down to the smallest class of 0.1-2 kbp. When the clustering was taken into account, the actual number of DNA double-strand breaks (separated by at least 0.1 kbp) could be calculated and was found to be in the range 0.010-0.012 breaks/Mbp Gy(-1). This is two- to threefold higher than the apparent yield obtained by the FAR assay. The measured yield of double-strand breaks as a function of LET is compared with theoretical Monte Carlo calculations that simulate the track structure of energy depositions from helium ions as they interact with the 30-nm chromatin fiber. When the calculation is performed to include fragments larger than 0.1 kbp (to correspond to the experimental measurements), there is good agreement between experiment and theory.
authors.affiliation: Lawrence Berkeley National Laboratory, Life Sciences Division, Department of Radiation Biology and DNA Repair, Berkeley, California 94720, USA.
authors.forename: Björn
authors.initials: B
authors.lastname: Rydberg
authors.forename: Lawrence
authors.initials: L
authors.lastname: Heilbronn
authors.forename: William R
authors.initials: WR
authors.lastname: Holley
authors.forename: Markus
authors.initials: M
authors.lastname: Löbrich
authors.forename: Cary
authors.initials: C
authors.lastname: Zeitlin
authors.forename: Aloke
authors.initials: A
authors.lastname: Chatterjee
authors.forename: Priscilla K
authors.initials: PK
authors.lastname: Cooper
mesh_terms: D002478:Cells, Cultured; D017357:Cyclotrons; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D005347:Fibroblasts / Q000187:drug effects*; D006371:Helium / Q000633:toxicity*; D006801:Humans; D009690:Nucleic Acid Conformation
chemical_list: D006371:Helium; D004247:DNA