Urinary n7-(1-hydroxy-3-buten-2-yl) guanine adducts in humans: Temporal stability and association with smoking

Caitlin C. Jokipii Krueger, Guru Madugundu, Amanda Degner, Yesha Patel, Daniel O. Stram, Timothy R. Church, Natalia Tretyakova

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

1,3-Butadiene (BD) is a known human carcinogen found in cigarette smoke, automobile exhaust, and urban air. Workers occupationally exposed to BD in the workplace have an increased incidence of leukemia and lymphoma. BD undergoes cytochrome P450-mediated metabolic activation to 3,4-epoxy-1-butene (EB), 1,2,3,4-diepoxybutane (DEB) and 1,2-dihydroxy-3,4-epoxybutane (EBD), which form covalent adducts with DNA. We have previously reported a quantitative nanoLC/ESI+-HRMS3 method for urinary N7-(1-hydroxy-3-buten-2-yl) guanine (EB-GII) adducts as a mechanism-based biomarker of BD exposure. In the present study, the method was updated to include high throughput 96-well solid phase extraction (SPE) and employed to establish urinary EB-GII biomarker stability and association with smoking. Urinary EB-GII levels were measured bimonthly for 1 year in 19 smokers to determine whether single adduct measurement provides reliable levels of EB-GII in an individual smoker. In addition, association of EB-GII with smoking was studied in 17 individuals participating in a smoking cessation program. EB-GII levels decreased 34% upon smoking cessation, indicating that it is associated with smoking status, but may also originate from sources other than exposure to cigarette smoke.

Original languageEnglish (US)
Pages (from-to)19-26
Number of pages8
JournalMutagenesis
Volume35
Issue number1
DOIs
StatePublished - Feb 13 2020

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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