2 research outputs found
Isotope Dilution nanoLC/ESI<sup>+</sup>‑HRMS<sup>3</sup> Quantitation of Urinary N7-(1-Hydroxy-3-buten-2-yl) Guanine Adducts in Humans and Their Use as Biomarkers of Exposure to 1,3-Butadiene
1,3-Butadiene
(BD) is an important industrial and environmental
chemical classified as a known human carcinogen. Occupational exposure
to BD in the polymer and monomer industries is associated with an
increased incidence of lymphoma. BD is present in automobile exhaust,
cigarette smoke, and forest fires, raising concern about potential
exposure of the general population to this carcinogen. Following inhalation
exposure, BD is bioactivated to 3,4-epoxy-1-butene (EB). If not detoxified,
EB is capable of modifying guanine and adenine bases of DNA to form
nucleobase adducts, which interfere with accurate DNA replication
and cause cancer-initiating mutations. We have developed a nanoLC/ESI<sup>+</sup>-HRMS<sup>3</sup> methodology for N7-(1-hydroxy-3-buten-2-yl)
guanine (EB-GII) adducts in human urine (limit of detection: 0.25
fmol/mL urine; limit of quantitation: 1.0 fmol/mL urine). This new
method was successfully used to quantify EB-GII in urine of F344 rats
treated with 0–200 ppm of BD, occupationally exposed workers,
and smokers belonging to two different ethnic groups. EB-GII amounts
increased in a dose-dependent manner in urine of laboratory rats exposed
to 0, 62.5, or 200 ppm of BD. Urinary EB-GII levels were significantly
increased in workers occupationally exposed to 0.1–2.2 ppm
of BD (1.25 ± 0.51 pg/mg of creatinine) as compared to administrative
controls exposed to <0.01 ppm of BD (0.22 ± 0.08 and pg/mg
of creatinine) (<i>p</i> = 0.0024), validating the use of
EB-GII as a biomarker of human exposure to BD. EB-GII was also detected
in smokers’ urine with European American smokers excreting
significantly higher amounts of EB-GII than African American smokers
(0.48 ± 0.09 vs 0.12 ± 0.02 pg/mg of creatinine, <i>p</i> = 3.1 × 10<sup>–7</sup>). Interestingly, small
amounts of EB-GII were observed in animals and humans with no known
exposure to BD, providing preliminary evidence for its endogenous
formation. Urinary EB-GII adduct levels and urinary mercapturic acids
of BD (MHBMA, DHBMA) were compared in a genotyped multiethnic smoker
cohort
Additional file 2: Table S1. of Sex and ethnic/racial-specific risk factors for gallbladder disease
Distribution of Risk Factors among MEC participants by sex and race/ethnicity. This table shows the distribution of risk factors in the MEC by sex and race/ethnicity. (DOCX 16 kb