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Significant disparity in base and sugar damage in DNA by neutron and electron irradiation

Published

Author(s)

Pawel Jaruga, Jeffrey S. Nico, Lisa R. Karam, Olga Timofeeva, William Blakely, M Miral Dizdar, D Pang

Abstract

In this study a comparison of the effects of high-LET neutrons with low-LET electrons on irradiation of aqueous DNA solutions was investigated to characterize for potential neutron signatures on DNA damage induction. Ionizing radiations generate numerous lesions in DNA including sugar, base, base and sugar damage (i.e., 8,5'-cyclopurine-2'-deoxynucleosides), DNA-protein cross-links, 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 irradiated with 0 to 80 Gy by low-LET electrons (10 Gy/min) and high-LET neutrons (≈ 0.16 Gy/h), the later formed by spontaneous 252Cf 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 neutrons were approximately 50 % less effective at a given dose as compared to electrons. Electron irradiation resulted in an exponential increase in S-cdA and R-cdA with dose, whereas neutrons 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 mechanisms of DNA damage by high- and low-LET radiation, leading to enhanced understanding of the potential biological effects of these radiations.
Citation
Journal of Radiation Research

Keywords

electron LINAC irradiation, 252Cf decay fission neutrons, 8-Hydroxy-2’-deoxyguanosine, (5’R)-8, 5’- cyclo-2’-deoxyadenosine, and (5’S)-8, 5’-cyclo-2’-deoxyadenosine, liquid chromatography-isotope- dilution tandem mass spectrometry, relative biological effectiveness
Created July 1, 2014, Updated January 27, 2020