Abstract

Reactive oxygen species (ROS) are generated in cells either by aerobic metabolism or by exposure to ionizing radiation and other oxidizing agents. They can damage cellular components by a radical-mediated mechanism. The resulting damaged products of nucleic acids have been implicated in cancer, neurological disorder, and natural processes of aging. Here we propose to develop sensitive mass spectrometric methods to characterize the structures and to quantify the amounts of oxidative DNA and RNA lesions, and there is a strong prospect that we will find new lesions. We also propose to study the chemical and biological properties of those oxidative lesions via mass spectrometry. Molecular modeling, organic synthesis, and other spectroscopic techniques will also be employed to answer those questions. The outcome of the research proposed here will provide better understanding of the biological consequences of oxidative damage on nucleic acids by ROS and their implications in human health.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA096906-03
Application #
6771092
Study Section
Special Emphasis Panel (ZRG1-BECM (01))
Program Officer
Knowlton, John R
Project Start
2002-07-01
Project End
2007-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
3
Fiscal Year
2004
Total Cost
$178,127
Indirect Cost

  Institution

Name
University of California Riverside
Department
Chemistry
Type
Schools of Earth Sciences/Natur
DUNS #
627797426
City
Riverside
State
CA
Country
United States
Zip Code
92521

  Publications

Wang, Hongxia; Wang, Yinsheng (2009) 6-Thioguanine perturbs cytosine methylation at the CpG dinucleotide site by DNA methyltransferases in vitro and acts as a DNA demethylating agent in vivo. Biochemistry 48:2290-9
Cao, Huachuan; Wang, Yinsheng (2009) Fragmentation of isomeric intrastrand crosslink lesions of DNA in an ion-trap mass spectrometer. J Am Soc Mass Spectrom 20:611-7
Yuan, Bifeng; Cao, Huachuan; Jiang, Yong et al. (2008) Efficient and accurate bypass of N2-(1-carboxyethyl)-2'-deoxyguanosine by DinB DNA polymerase in vitro and in vivo. Proc Natl Acad Sci U S A 105:8679-84
Cao, Huachuan; Hearst, John E; Corash, Laurence et al. (2008) LC-MS/MS for the detection of DNA interstrand cross-links formed by 8-methoxypsoralen and UVA irradiation in human cells. Anal Chem 80:2932-8
Wang, Yinsheng (2008) Bulky DNA lesions induced by reactive oxygen species. Chem Res Toxicol 21:276-81
Hong, Haizheng; Cao, Huachuan; Wang, Yinsheng (2007) Formation and genotoxicity of a guanine-cytosine intrastrand cross-link lesion in vivo. Nucleic Acids Res 35:7118-27
Jiang, Yong; Hong, Haizheng; Cao, Huachuan et al. (2007) In vivo formation and in vitro replication of a guanine-thymine intrastrand cross-link lesion. Biochemistry 46:12757-63
Cao, Huachuan; Jiang, Yong; Wang, Yinsheng (2007) Stereospecific synthesis and characterization of oligodeoxyribonucleotides containing an N2-(1-carboxyethyl)-2'-deoxyguanosine. J Am Chem Soc 129:12123-30
Zeng, Yu; Wang, Yinsheng (2007) UVB-Induced formation of intrastrand cross-link products of DNA in MCF-7 cells treated with 5-bromo-2'-deoxyuridine. Biochemistry 46:8189-95
Gu, Chunang; Wang, Yinsheng (2007) In vitro replication and thermodynamic studies of methylation and oxidation modifications of 6-thioguanine. Nucleic Acids Res 35:3693-704

Showing the most recent 10 out of 27 publications