Program Official

Principal Investigator

Robert J.
Awardee Organization

University Of Minnesota
United States

Fiscal Year
Activity Code
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

DNA adductomics of the urinary system

The goal of our research is to chemically characterize DNA adducts associated with specific human cancers. We will link this structural information to novel mutational patterns identified during this research. These melded data should facilitate significantly the identification of environmental, dietary and endogenous agents responsible for human cancers. The proposed research focuses on renal and urological cancers; specifically, clear-cell renal cell carcinomas, carcinomas of the upper urinary tract and bladder cancer. Additionally, we will attempt to detect and, if possible, quantify single or multiple DNA adducts found in exfoliated urinary cells as an initial step in developing a noninvasive biomarker for carcinogen screening. In this research, we utilize sensitive, mass spectrometry techniques to detect and quantify multiple DNA adducts in target tissues and urinary cells. For screening purposes, we will employ ultraperformance liquid chromatography/multistage scan mass spectrometry (UPLC/MSn), using a linear quadrupole ion trap mass spectrometer. The use of UPLC/MSn permits quantitation of known adducts and characterization of unknown adducts, the latter by acquiring MS3 scan stage product ion spectra. We have employed this approach successfully to identify single and multiple DNA adducts in human tissues, saliva, and exfoliated urinary cells. In Aim 1, we use data-dependent and independent scanning methods to optimize detection of DNA adducts derived from genotoxins found in tobacco smoke and in the diet; also from electrophiles that are produced endogenously by oxidative processes. In Aim 2, we employ targeted as well as data-dependent and independent “adductomics” approaches, using UPLC/MSn to screen DNA adducts formed in the kidney, upper urothelial tract, bladder, and cells in the urine of patients with target cancers. In Aim 3, we conduct deep sequencing of DNA isolated from tumor and non-tumor tissues to identify mutational patterns that may be linked to specific DNA adducts, chemical exposures or aberrant endogenous processes. Our research has significant implications for public health. DNA adduct and mutational data are of high translational impact and provide an understanding of exposures to hazardous chemicals that can initiate cancer in humans. By linking these methods, we create a molecular approach that provides clues to the identity of environmental, dietary and endogenous carcinogens and establishes biomarkers of exposure that can be used in epidemiologic studies to identify populations at risk. Once identified, pragmatic measures can be taken to reduce human exposure to these chemicals, by changes in life-style and/or diet, which are probably the most efficient means of chemoprevention.


  • Walmsley SJ, Guo J, Wang J, Villalta PW, Turesky RJ. Methods and Challenges for Computational Data Analysis for DNA Adductomics. Chemical research in toxicology. 2019 Nov 18;32(11):2156-2168. Epub 2019 Nov 6. PMID: 31549505
  • Yun BH, Guo J, Turesky RJ. Formalin-Fixed Paraffin-Embedded Tissues-An Untapped Biospecimen for Biomonitoring DNA Adducts by Mass Spectrometry. Toxics. 2018 Jun 1;6. (2). PMID: 29865161
  • Chen CH, Grollman AP, Huang CY, Shun CT, Sidorenko VS, Hashimoto K, Moriya M, Turesky RJ, Yun BH, Tsai K, Wu S, Chuang PY, Tang CH, Yang WH, Tzai TS, Tsai YS, Dickman KG, Pu YS. Additive Effects of Arsenic and Aristolochic Acid in Chemical Carcinogenesis of Upper Urinary Tract Urothelium. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2021 Feb;30(2):317-325. Epub 2020 Dec 4. PMID: 33277322
  • Yun BH, Bellamri M, Rosenquist TA, Turesky RJ. Method for Biomonitoring DNA Adducts in Exfoliated Urinary Cells by Mass Spectrometry. Analytical chemistry. 2018 Aug 21;90(16):9943-9950. Epub 2018 Jul 30. PMID: 30001485
  • Bellamri M, Yao L, Bonala R, Johnson F, Von Weymarn LB, Turesky RJ. Bioactivation of the tobacco carcinogens 4-aminobiphenyl (4-ABP) and 2-amino-9H-pyrido[2,3-b]indole (AαC) in human bladder RT4 cells. Archives of toxicology. 2019 Jul;93(7):1893-1902. Epub 2019 Jun 15. PMID: 31203411
  • Guo J, Villalta PW, Weight CJ, Bonala R, Johnson F, Rosenquist TA, Turesky RJ. Targeted and Untargeted Detection of DNA Adducts of Aromatic Amine Carcinogens in Human Bladder by Ultra-Performance Liquid Chromatography-High-Resolution Mass Spectrometry. Chemical research in toxicology. 2018 Dec 17;31(12):1382-1397. Epub 2018 Nov 19. PMID: 30387604
  • Ragi N, Walmsley SJ, Jacobs FC, Rosenquist TA, Sidorenko VS, Yao L, Maertens LA, Weight CJ, Balbo S, Villalta PW, Turesky RJ. Screening DNA Damage in the Rat Kidney and Liver by Untargeted DNA Adductomics. Chemical research in toxicology. 2024 Feb 19;37(2):340-360. Epub 2024 Jan 9. PMID: 38194517
  • Guo J, Villalta PW, Turesky RJ. Data-Independent Mass Spectrometry Approach for Screening and Identification of DNA Adducts. Analytical chemistry. 2017 Nov 7;89(21):11728-11736. Epub 2017 Oct 18. PMID: 28977750
  • Bellamri M, Walmsley SJ, Brown C, Brandt K, Konorev D, Day A, Wu CF, Wu MT, Turesky RJ. DNA Damage and Oxidative Stress of Tobacco Smoke Condensate in Human Bladder Epithelial Cells. Chemical research in toxicology. 2022 Oct 17;35(10):1863-1880. Epub 2022 Jul 25. PMID: 35877975
  • Bellamri M, Brandt K, Brown CV, Wu MT, Turesky RJ. Cytotoxicity and genotoxicity of the carcinogen aristolochic acid I (AA-I) in human bladder RT4 cells. Archives of toxicology. 2021 Jun;95(6):2189-2199. Epub 2021 May 3. PMID: 33938965
  • Guo J, Turesky RJ. Emerging Technologies in Mass Spectrometry-Based DNA Adductomics. High-throughput. 2019 May 14;8. (2). PMID: 31091740
  • Hwa Yun B, Guo J, Bellamri M, Turesky RJ. DNA adducts: Formation, biological effects, and new biospecimens for mass spectrometric measurements in humans. Mass spectrometry reviews. 2020 Mar;39(1-2):55-82. Epub 2018 Jun 11. PMID: 29889312
  • Guo J, Koopmeiners JS, Walmsley SJ, Villalta PW, Yao L, Murugan P, Tejpaul R, Weight CJ, Turesky RJ. The Cooked Meat Carcinogen 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine Hair Dosimeter, DNA Adductomics Discovery, and Associations with Prostate Cancer Pathology Biomarkers. Chemical research in toxicology. 2022 May 16;35(5):703-730. Epub 2022 Apr 21. PMID: 35446561
  • Chen H, Krishnamachari S, Guo J, Yao L, Murugan P, Weight CJ, Turesky RJ. Quantitation of Lipid Peroxidation Product DNA Adducts in Human Prostate by Tandem Mass Spectrometry: A Method That Mitigates Artifacts. Chemical research in toxicology. 2019 Sep 16;32(9):1850-1862. Epub 2019 Aug 16. PMID: 31361128
  • Yun BH, Xiao S, Yao L, Krishnamachari S, Rosenquist TA, Dickman KG, Grollman AP, Murugan P, Weight CJ, Turesky RJ. A Rapid Throughput Method To Extract DNA from Formalin-Fixed Paraffin-Embedded Tissues for Biomonitoring Carcinogenic DNA Adducts. Chemical research in toxicology. 2017 Dec 18;30(12):2130-2139. Epub 2017 Nov 27. PMID: 29120619
  • Walmsley SJ, Guo J, Murugan P, Weight CJ, Wang J, Villalta PW, Turesky RJ. Comprehensive Analysis of DNA Adducts Using Data-Independent wSIM/MS2 Acquisition and wSIM-City. Analytical chemistry. 2021 Apr 27;93(16):6491-6500. Epub 2021 Apr 12. PMID: 33844920
  • Peterson LA, Balbo S, Fujioka N, Hatsukami DK, Hecht SS, Murphy SE, Stepanov I, Tretyakova NY, Turesky RJ, Villalta PW. Applying Tobacco, Environmental, and Dietary-Related Biomarkers to Understand Cancer Etiology and Evaluate Prevention Strategies. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2020 Oct;29(10):1904-1919. Epub 2020 Feb 12. PMID: 32051197
  • Guo J, Turesky RJ, Tarifa A, DeCaprio AP, Cooke MS, Walmsley SJ, Villalta PW. Development of a DNA Adductome Mass Spectral Database. Chemical research in toxicology. 2020 Apr 20;33(4):852-854. Epub 2020 Mar 30. PMID: 32223224