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Significant disparity in base and sugar damage in DNA resulting from neutron and electron irradiation.
J Radiat Res 2014; 55(6):1081-8JR

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+Show Affiliations

Department of Radiation Medicine, Georgetown University Hospital, 3800 Reservoir Road, LL Bles, Washington, DC 20007, USA pangd@georgetown.edu.Radiation Physics Division, National Institute of Standards and Technology, Gaithersburg, MD 20899, USA.Radiation Physics Division, National Institute of Standards and Technology, Gaithersburg, MD 20899, USA.Department of Radiation Medicine, Georgetown University Hospital, 3800 Reservoir Road, LL Bles, Washington, DC 20007, USA.Scientific Research Department, Armed Forces Radiobiological Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20889, USA.Department of Radiation Medicine, Georgetown University Hospital, 3800 Reservoir Road, LL Bles, Washington, DC 20007, USA.Biomolecular Measurement Division, National Institute of Standards and Technology, Gaithersburg, MD 20899, USA.Biomolecular Measurement Division, National Institute of Standards and Technology, Gaithersburg, MD 20899, USA.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25034731

Citation

Pang, Dalong, et al. "Significant Disparity in Base and Sugar Damage in DNA Resulting From Neutron and Electron Irradiation." Journal of Radiation Research, vol. 55, no. 6, 2014, pp. 1081-8.
Pang D, Nico JS, Karam L, et al. Significant disparity in base and sugar damage in DNA resulting from neutron and electron irradiation. J Radiat Res. 2014;55(6):1081-8.
Pang, D., Nico, J. S., Karam, L., Timofeeva, O., Blakely, W. F., Dritschilo, A., ... Jaruga, P. (2014). Significant disparity in base and sugar damage in DNA resulting from neutron and electron irradiation. Journal of Radiation Research, 55(6), pp. 1081-8. doi:10.1093/jrr/rru059.
Pang D, et al. Significant Disparity in Base and Sugar Damage in DNA Resulting From Neutron and Electron Irradiation. J Radiat Res. 2014;55(6):1081-8. PubMed PMID: 25034731.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Significant disparity in base and sugar damage in DNA resulting from neutron and electron irradiation. AU - Pang,Dalong, AU - Nico,Jeffrey S, AU - Karam,Lisa, AU - Timofeeva,Olga, AU - Blakely,William F, AU - Dritschilo,Anatoly, AU - Dizdaroglu,Miral, AU - Jaruga,Pawel, Y1 - 2014/07/17/ PY - 2014/7/19/entrez PY - 2014/7/19/pubmed PY - 2015/10/20/medline KW - (5′R)-8,5′-cyclo-2′-deoxyadenosine KW - 252Cf decay fission neutrons KW - 8-hydroxy-2′-deoxyguanosine KW - and (5′S)-8,5′-cyclo-2′-deoxyadenosine KW - electron LINAC irradiation KW - liquid chromatography–isotope-dilution tandem mass spectrometry KW - relative biological effectiveness SP - 1081 EP - 8 JF - Journal of radiation research JO - J. Radiat. Res. VL - 55 IS - 6 N2 - 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. SN - 1349-9157 UR - https://www.unboundmedicine.com/medline/citation/25034731/Significant_disparity_in_base_and_sugar_damage_in_DNA_resulting_from_neutron_and_electron_irradiation L2 - https://academic.oup.com/jrr/article-lookup/doi/10.1093/jrr/rru059 DB - PRIME DP - Unbound Medicine ER -