PMID- 24531806 OWN - NLM STAT- MEDLINE DCOM- 20140804 LR - 20211021 IS - 1460-2180 (Electronic) IS - 0143-3334 (Print) IS - 0143-3334 (Linking) VI - 35 IP - 6 DP - 2014 Jun TI - Bis-butanediol-mercapturic acid (bis-BDMA) as a urinary biomarker of metabolic activation of butadiene to its ultimate carcinogenic species. PG - 1371-8 LID - 10.1093/carcin/bgu047 [doi] AB - Human carcinogen 1,3-butadiene (BD) undergoes metabolic activation to 3,4-epoxy-1-butene (EB), hydroxymethylvinyl ketone (HMVK), 3,4-epoxy-1,2-butanediol (EBD) and 1,2,3,4-diepoxybutane (DEB). Among these, DEB is by far the most genotoxic metabolite and is considered the ultimate carcinogenic species of BD. We have shown previously that BD-exposed laboratory mice form 8- to 10-fold more DEB-DNA adducts than rats exposed at the same conditions, which may be responsible for the enhanced sensitivity of mice to BD-mediated cancer. In the present study, we have identified 1,4-bis-(N-acetyl-L-cystein-S-yl)butane-2,3-diol (bis-BDMA) as a novel DEB-specific urinary biomarker. Isotope dilution high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry was employed to quantify bis-BDMA and three other BD-mercapturic acids, 2-(N-acetyl-L-cystein-S-yl)-1-hydroxybut-3-ene/1-(N-acetyl-L-cystein-S-yl)-2-hydroxy-but-3-ene (MHBMA, from EB), 4-(N-acetyl-L-cystein-S-yl)-1,2-dihydroxybutane (DHBMA, from HMVK) and 4-(N-acetyl-L-cystein-S-yl)-1,2,3-trihydroxybutane (THBMA, from EBD), in urine of confirmed smokers, occupationally exposed workers and BD-exposed laboratory rats. Bis-BDMA was formed in a dose-dependent manner in urine of rats exposed to 0-200 p.p.m. BD by inhalation, although it was a minor metabolite (1%) as compared with DHBMA (47%) and THBMA (37%). In humans, DHBMA was the most abundant BD-mercapturic acid excreted (93%), followed by THBMA (5%) and MHBMA (2%), whereas no bis-BDMA was detected. These results reveal significant differences in metabolism of BD between rats and humans. CI - (c) The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com. FAU - Kotapati, Srikanth AU - Kotapati S AD - Department of Medicinal Chemistry and the Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA, Sealy Center for Environmental Health and Medicine (SCEHM) and the Department of Preventive Medicine and Community Health, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA, Department of Pathology, University of Vermont, Burlington, VT 05405, USA and Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. FAU - Sangaraju, Dewakar AU - Sangaraju D AD - Department of Medicinal Chemistry and the Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA, Sealy Center for Environmental Health and Medicine (SCEHM) and the Department of Preventive Medicine and Community Health, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA, Department of Pathology, University of Vermont, Burlington, VT 05405, USA and Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. FAU - Esades, Amanda AU - Esades A AD - Department of Medicinal Chemistry and the Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA, Sealy Center for Environmental Health and Medicine (SCEHM) and the Department of Preventive Medicine and Community Health, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA, Department of Pathology, University of Vermont, Burlington, VT 05405, USA and Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. FAU - Hallberg, Lance AU - Hallberg L AD - Sealy Center for Environmental Health and Medicine (SCEHM) and the Department of Preventive Medicine and Community Health, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA. FAU - Walker, Vernon E AU - Walker VE AD - Department of Pathology, University of Vermont, Burlington, VT 05405, USA and. FAU - Swenberg, James A AU - Swenberg JA AD - Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. FAU - Tretyakova, Natalia Y AU - Tretyakova NY AD - Department of Medicinal Chemistry and the Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA, Sealy Center for Environmental Health and Medicine (SCEHM) and the Department of Preventive Medicine and Community Health, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA, Department of Pathology, University of Vermont, Burlington, VT 05405, USA and Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA trety001@umn.edu. LA - eng GR - P30 ES010126/ES/NIEHS NIH HHS/United States GR - CA-77598/CA/NCI NIH HHS/United States GR - P30 CA077598/CA/NCI NIH HHS/United States GR - CA-138338/CA/NCI NIH HHS/United States GR - ES012689-05/ES/NIEHS NIH HHS/United States GR - 5-51624/PHS HHS/United States GR - P42 ES005948/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20140214 PL - England TA - Carcinogenesis JT - Carcinogenesis JID - 8008055 RN - 0 (Biomarkers) RN - 0 (Butadienes) RN - 0 (Carcinogens) RN - 0 (DNA Adducts) RN - JSD5FGP5VD (1,3-butadiene) SB - IM MH - Animals MH - Biomarkers/metabolism/urine MH - Butadienes/administration & dosage/chemistry/*metabolism/urine MH - Carcinogens/administration & dosage/chemistry/*metabolism MH - Chromatography, High Pressure Liquid MH - DNA Adducts/drug effects/metabolism MH - Dose-Response Relationship, Drug MH - Female MH - Humans MH - Inhalation MH - Liver/drug effects/metabolism MH - Male MH - Metabolic Networks and Pathways MH - Occupational Exposure MH - Rats MH - Smoking MH - Tandem Mass Spectrometry PMC - PMC4043237 EDAT- 2014/02/18 06:00 MHDA- 2014/08/05 06:00 PMCR- 2015/06/01 CRDT- 2014/02/18 06:00 PHST- 2014/02/18 06:00 [entrez] PHST- 2014/02/18 06:00 [pubmed] PHST- 2014/08/05 06:00 [medline] PHST- 2015/06/01 00:00 [pmc-release] AID - bgu047 [pii] AID - 10.1093/carcin/bgu047 [doi] PST - ppublish SO - Carcinogenesis. 2014 Jun;35(6):1371-8. doi: 10.1093/carcin/bgu047. Epub 2014 Feb 14.