Article pubs.acs.org/crt
Isotope Dilution nanoLC/ESI+‑HRMS3 Quantitation of Urinary N7-(1Hydroxy-3-buten-2-yl) Guanine Adducts in Humans and Their Use as Biomarkers of Exposure to 1,3-Butadiene Dewakar Sangaraju,† Emily J. Boldry,† Yesha M. Patel,¶ Vernon Walker,§ Irina Stepanov,‡ Daniel Stram,¶ Dorothy Hatsukami,⊥ and Natalia Tretyakova*,† †
Department of Medicinal Chemistry and Masonic Cancer Center, ‡School of Public Health, Division of Environmental Health Sciences and Masonic Cancer Center, and ⊥Department of Psychiatry and Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, United States ¶ Division of Biostatistics, Keck School of Medicine and Children’s Cancer Group, University of Southern California, Los Angeles, California 90089, United States § Department of Pathology and Laboratory Medicine, University of Vermont, Burlington, Vermont 05405, United States S Supporting Information *
ABSTRACT: 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 3,4epoxy-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+-HRMS3 methodology for N7-(1hydroxy-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
