TY - JOUR
T1 - Urinary n7-(1-hydroxy-3-buten-2-yl) guanine adducts in humans
T2 - Temporal stability and association with smoking
AU - Jokipii Krueger, Caitlin C.
AU - Madugundu, Guru
AU - Degner, Amanda
AU - Patel, Yesha
AU - Stram, Daniel O.
AU - Church, Timothy R.
AU - Tretyakova, Natalia
N1 - Funding Information:
This work was supported by the National Cancer Institute at the National Institutes of Health [CA 138338 and CA 100670 to N.Y.T.]
Publisher Copyright:
© 2019 The Author(s) 2019. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society.
PY - 2020/2/13
Y1 - 2020/2/13
N2 - 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.
AB - 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.
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U2 - 10.1093/mutage/gez030
DO - 10.1093/mutage/gez030
M3 - Article
C2 - 31702786
AN - SCOPUS:85079344295
SN - 0267-8357
VL - 35
SP - 19
EP - 26
JO - Mutagenesis
JF - Mutagenesis
IS - 1
ER -
