PMID- 24867429 OWN - NLM STAT- MEDLINE DCOM- 20150417 LR - 20240326 IS - 1879-1123 (Electronic) IS - 1044-0305 (Print) IS - 1044-0305 (Linking) VI - 25 IP - 7 DP - 2014 Jul TI - NanoLC/ESI+ HRMS3 quantitation of DNA adducts induced by 1,3-butadiene. PG - 1124-35 LID - 10.1007/s13361-014-0916-x [doi] AB - Human exposure to 1,3-butadiene (BD) present in automobile exhaust, cigarette smoke, and forest fires is of great concern because of its potent carcinogenicity. The adverse health effects of BD are mediated by its epoxide metabolites such as 3,4-epoxy-1-butene (EB), which covalently modify genomic DNA to form promutagenic nucleobase adducts. Because of their direct role in cancer, BD-DNA adducts can be used as mechanism-based biomarkers of BD exposure. In the present work, a mass spectrometry-based methodology was developed for accurate, sensitive, and precise quantification of EB-induced N-7-(1-hydroxy-3-buten-2-yl) guanine (EB-GII) DNA adducts in vivo. In our approach, EB-GII adducts are selectively released from DNA backbone by neutral thermal hydrolysis, followed by ultrafiltration, offline HPLC purification, and isotope dilution nanoLC/ESI(+)-HRMS(3) analysis on an Orbitrap Velos mass spectrometer. Following method validation, EB-GII lesions were quantified in human fibrosarcoma (HT1080) cells treated with micromolar concentrations of EB and in liver tissues of rats exposed to sub-ppm concentrations of BD (0.5-1.5 ppm). EB-GII concentrations increased linearly from 1.15 +/- 0.23 to 10.11 +/- 0.45 adducts per 10(8) nucleotides in HT1080 cells treated with 0.5-10 muM EB. EB-GII concentrations in DNA of laboratory rats exposed to 0.5, 1.0, and 1.5 ppm BD were 0.17 +/- 0.05, 0.33 +/- 0.08, and 0.50 +/- 0.04 adducts per 10(8) nucleotides, respectively [corrected]. We also used the new method to determine the in vivo half-life of EB-GII adducts in rat liver DNA (2.20 +/- 0.12 d) and to detect EB-GII in human blood DNA. To our knowledge, this is the first application of nanoLC/ESI(+)-HRMS(3) Orbitrap methodology to quantitative analysis of DNA adducts in vivo. FAU - Sangaraju, Dewakar AU - Sangaraju D AD - Department of Medicinal Chemistry and the Masonic Cancer Center, University of Minnesota, Minneapolis, MN, 55455, USA. FAU - Villalta, Peter W AU - Villalta PW FAU - Wickramaratne, Susith AU - Wickramaratne S FAU - Swenberg, James AU - Swenberg J FAU - Tretyakova, Natalia AU - Tretyakova N LA - eng GR - CA-77598/CA/NCI NIH HHS/United States GR - P30 CA077598/CA/NCI NIH HHS/United States GR - S10 RR024618/RR/NCRR NIH HHS/United States GR - 1P01 CA138338/CA/NCI NIH HHS/United States GR - HHSN261200644002/PHS HHS/United States GR - N01 CN064402/CN/NCI NIH HHS/United States GR - S10-RR-024618/RR/NCRR NIH HHS/United States GR - P01 CA138338/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20140528 PL - United States TA - J Am Soc Mass Spectrom JT - Journal of the American Society for Mass Spectrometry JID - 9010412 RN - 0 (Butadienes) RN - 0 (DNA Adducts) RN - 0 (Epoxy Compounds) RN - 478ERR5NKR (3,4-epoxy-1-butene) RN - JSD5FGP5VD (1,3-butadiene) SB - IM EIN - J Am Soc Mass Spectrom. 2014 Sep;25(9):1674 MH - Adult MH - Animals MH - Butadienes/*chemistry/metabolism MH - Cell Line, Tumor MH - DNA Adducts/*analysis/*chemistry/metabolism MH - Environmental Exposure/*analysis MH - Epoxy Compounds/analysis/chemistry/metabolism MH - Female MH - Humans MH - Liver/chemistry/drug effects MH - Male MH - Middle Aged MH - Rats MH - Rats, Inbred F344 MH - Reproducibility of Results MH - Sensitivity and Specificity MH - Spectrometry, Mass, Electrospray Ionization/*methods MH - Young Adult PMC - PMC5076477 MID - NIHMS822244 EDAT- 2014/05/29 06:00 MHDA- 2015/04/18 06:00 PMCR- 2016/10/24 CRDT- 2014/05/29 06:00 PHST- 2014/01/16 00:00 [received] PHST- 2014/04/14 00:00 [accepted] PHST- 2014/04/11 00:00 [revised] PHST- 2014/05/29 06:00 [entrez] PHST- 2014/05/29 06:00 [pubmed] PHST- 2015/04/18 06:00 [medline] PHST- 2016/10/24 00:00 [pmc-release] AID - 10.1007/s13361-014-0916-x [doi] PST - ppublish SO - J Am Soc Mass Spectrom. 2014 Jul;25(7):1124-35. doi: 10.1007/s13361-014-0916-x. Epub 2014 May 28.