title: Significant disparity in base and sugar damage in DNA resulting from neutron and electron irradiation.
abstract: In this study, a comparison of the effects of neutron and electron irradiation of aqueous DNA solutions was investigated to characterize potential neutron signatures in DNA damage induction. Ionizing radiation generates numerous lesions in DNA, including base and sugar lesions, lesions involving base-sugar combinations (e.g. 8,5'-cyclopurine-2'-deoxynucleosides) and DNA-protein cross-links, as well as single- and double-strand breaks and clustered damage. The characteristics of damage depend on the linear energy transfer (LET) of the incident radiation. Here we investigated DNA damage using aqueous DNA solutions in 10 mmol/l phosphate buffer from 0-80 Gy by low-LET electrons (10 Gy/min) and the specific high-LET (∼0.16 Gy/h) neutrons formed by spontaneous (252)Cf decay fissions. 8-hydroxy-2'-deoxyguanosine (8-OH-dG), (5'R)-8,5'-cyclo-2'-deoxyadenosine (R-cdA) and (5'S)-8,5'-cyclo-2'-deoxyadenosine (S-cdA) were quantified using liquid chromatography-isotope-dilution tandem mass spectrometry to demonstrate a linear dose dependence for induction of 8-OH-dG by both types of radiation, although neutron irradiation was ∼50% less effective at a given dose compared with electron irradiation. Electron irradiation resulted in an exponential increase in S-cdA and R-cdA with dose, whereas neutron irradiation induced substantially less damage and the amount of damage increased only gradually with dose. Addition of 30 mmol/l 2-amino-2-(hydroxymethyl)-1,3-propanediol (TRIS), a free radical scavenger, to the DNA solution before irradiation reduced lesion induction to background levels for both types of radiation. These results provide insight into the mechanisms of DNA damage by high-LET (252)Cf decay neutrons and low-LET electrons, leading to enhanced understanding of the potential biological effects of these types of irradiation.
authors.affiliation: Department of Radiation Medicine, Georgetown University Hospital, 3800 Reservoir Road, LL Bles, Washington, DC 20007, USA pangd@georgetown.edu.
authors.forename: Dalong
authors.initials: D
authors.lastname: Pang
authors.affiliation: Radiation Physics Division, National Institute of Standards and Technology, Gaithersburg, MD 20899, USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Nico
authors.affiliation: Radiation Physics Division, National Institute of Standards and Technology, Gaithersburg, MD 20899, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Karam
authors.affiliation: Department of Radiation Medicine, Georgetown University Hospital, 3800 Reservoir Road, LL Bles, Washington, DC 20007, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Timofeeva
authors.affiliation: Scientific Research Department, Armed Forces Radiobiological Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20889, USA.
authors.forename: William F
authors.initials: WF
authors.lastname: Blakely
authors.affiliation: Department of Radiation Medicine, Georgetown University Hospital, 3800 Reservoir Road, LL Bles, Washington, DC 20007, USA.
authors.forename: Anatoly
authors.initials: A
authors.lastname: Dritschilo
authors.affiliation: Biomolecular Measurement Division, National Institute of Standards and Technology, Gaithersburg, MD 20899, USA.
authors.forename: Miral
authors.initials: M
authors.lastname: Dizdaroglu
authors.affiliation: Biomolecular Measurement Division, National Institute of Standards and Technology, Gaithersburg, MD 20899, USA.
authors.forename: Pawel
authors.initials: P
authors.lastname: Jaruga
mesh_terms: D000818:Animals; D002417:Cattle; D004247:DNA / Q000737:chemistry* / Q000528:radiation effects*; D004249:DNA Damage; D003839:Deoxyadenosines / Q000737:chemistry / Q000528:radiation effects; D004583:Electrons / Q000009:adverse effects; D066298:In Vitro Techniques; D018499:Linear Energy Transfer; D009502:Neutrons / Q000009:adverse effects; D053719:Tandem Mass Spectrometry
chemical_list: D003839:Deoxyadenosines; D004247:DNA
keywords: (5′R)-8,5′-cyclo-2′-deoxyadenosine; 252Cf decay fission neutrons; 8-hydroxy-2′-deoxyguanosine; and (5′S)-8,5′-cyclo-2′-deoxyadenosine; electron LINAC irradiation; liquid chromatography–isotope-dilution tandem mass spectrometry; relative biological effectiveness