Abstract

The long term objective of this research project is to formulate a set of rules that will predict both the type and probability of specific chemical alterations produced in chromatin DNA by the direct effects of ionizing radiation. Achievement of this objective is important to defining the risks associated with long term exposures to low doses of radiation: risks such as the induction of cancer or leukemia.
The specific aim i s to fully characterize the free radical processes by which ionizing radiation, through direct effects, alters the chemical structure of the nucleic acid bases. A full characterization entails 1. the identification of the pristine free radicals, 2. the monitoring of the subsequent reactions, 3. the measurement of the yield and destruction constants, and 4. the determination of the influence of the host matrix on radical formation, trapping, and subsequent reactions. The bases will be studied in the form of single crystals using electron spin resonance (ESR) and electron nuclear double resonance (ENDOR) spectroscopy. The free radical products and reactions will be studied over a temperature range of 4.2K to 300K. The series of crystals scheduled for study consist of simple derivatives of the common nucleic acid bases. An emphasis will be given to thymine and adenine derivatives as the work is targeted toward working out the distribution of free radical damage in a 1-methylthymine:adenosine co-crystalline complex.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA032546-12
Application #
3170431
Study Section
Radiation Study Section (RAD)
Project Start
1982-02-01
Project End
1990-01-31
Budget Start
1987-02-01
Budget End
1988-01-31
Support Year
12
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
University of Rochester
Department
Type
School of Medicine & Dentistry
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627

  Publications

Black, Paul J; Miller, Adam S; Hayes, Jeffrey J (2016) Radioresistance of GGG sequences to prompt strand break formation from direct-type radiation damage. Radiat Environ Biophys 55:411-422
Roginskaya, Marina; Mohseni, Reza; Moore, Terence J et al. (2014) Identification of the C4'-oxidized abasic site as the most abundant 2-deoxyribose lesion in radiation-damaged DNA using a novel HPLC-based approach. Radiat Res 181:131-7
Black, Paul J; Bernhard, William A (2012) Excess electron trapping in duplex DNA: long range transfer via stacked adenines. J Phys Chem B 116:13211-8
Peoples, Anita R; Lee, Jane; Weinfeld, Michael et al. (2012) Yields of damage to C4' deoxyribose and to pyrimidines in pUC18 by the direct effect of ionizing radiation. Nucleic Acids Res 40:6060-9
Black, Paul J; Bernhard, William A (2011) EPR detection of an electron scavenging contaminant in irradiated deoxyoligonucleotides: one-electron reduced benzoyl. J Phys Chem B 115:8009-13
Sharma, Kiran K K; Swarts, Steven G; Bernhard, William A (2011) Mechanisms of direct radiation damage to DNA: the effect of base sequence on base end products. J Phys Chem B 115:4843-55
Price, Charles S; Razskazovskiy, Yuriy; Bernhard, William A (2010) Factors affecting the yields of C1' and C5' oxidation products in radiation-damaged DNA: the indirect effect. Radiat Res 174:645-9
Peoples, Anita R; Mercer, Kermit R; Bernhard, William A (2010) What fraction of DNA double-strand breaks produced by the direct effect is accounted for by radical pairs? J Phys Chem B 114:9283-8
Sharma, Kiran K K; Tyagi, Rahul; Purkayastha, Shubhadeep et al. (2010) One-electron oxidation of DNA by ionizing radiation: competition between base-to-base hole-transfer and hole-trapping. J Phys Chem B 114:7672-80
Sharma, Kiran Kumar K; Bernhard, William A (2009) Direct damage to the backbone of DNA oligomers is influenced by the OH moiety at strand ends, by the type of base, and by context. J Phys Chem B 113:12839-43

Showing the most recent 10 out of 35 publications