PMID- 33693566 OWN - NLM STAT- MEDLINE DCOM- 20210929 LR - 20221207 IS - 1460-2180 (Electronic) IS - 0143-3334 (Print) IS - 0143-3334 (Linking) VI - 42 IP - 5 DP - 2021 May 28 TI - Ethnic differences in excretion of butadiene-DNA adducts by current smokers. PG - 694-704 LID - 10.1093/carcin/bgab020 [doi] AB - 1,3-Butadiene (BD) is a known human carcinogen used in the synthetic polymer industry and also found in cigarette smoke, automobile exhaust and wood burning smoke. BD is metabolically activated by cytochrome P450 monooxygenases (CYP) 2E1 and 2A6 to 3,4-epoxy-1-butene (EB), which can be detoxified by GST-catalyzed glutathione conjugation or hydrolysis. We have previously observed ethnic differences in urinary levels of EB-mercapturic acids in white, Japanese American and Native Hawaiian smokers. In the present study, similar analyses were extended to urinary BD-DNA adducts. BD-induced N7-(1-hydroxy-3-buten-2-yl) guanine (EB-GII) adducts were quantified in urine samples obtained from smokers and non-smokers belonging to three racial/ethnic groups: white, Japanese American and Native Hawaiian. After adjusting for sex, age, nicotine equivalents, body mass index and batch, we found that Japanese American smokers excreted significantly higher amounts of urinary EB-GII than whites [1.45 (95% confidence interval: 1.12-1.87) versus 0.68 (95% confidence interval: 0.52-0.85) fmol/ml urine, P = 4 x 10-5]. Levels of urinary EB-GII in Native Hawaiian smokers were not different from those in whites [0.67 (95% confidence interval: 0.51-0.84) fmol/ml urine, P = 0.938]. There were no racial/ethnic differences in urinary EB-GII adduct levels in non-smokers. Racial/ethnic differences in urinary EB-GII adduct levels in smokers could not be explained by GSTT1 gene deletion or CYP2A6 enzymatic activity. Urinary EB-GII adduct levels in smokers were significantly associated with concentrations of BD metabolite dihyroxybutyl mercapturic acid. Overall, our results reveal that urinary EB-GII adducts in smokers differ across racial/ethnic groups. Future studies are required to understand genetic and epigenetic factors that may be responsible for these differences. CI - (c) The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com. FAU - Jokipii Krueger, Caitlin C AU - Jokipii Krueger CC AD - Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA. AD - Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA. FAU - Park, S Lani AU - Park SL AD - Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96822, USA. FAU - Madugundu, Guru AU - Madugundu G AD - Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA. AD - Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA. FAU - Patel, Yesha AU - Patel Y AD - Department of Preventative Medicine, School of Medicine, University of Southern California, Los Angeles, CA 90089, USA. FAU - Le Marchand, Loic AU - Le Marchand L AD - Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96822, USA. FAU - Stram, Daniel O AU - Stram DO AD - Department of Preventative Medicine, School of Medicine, University of Southern California, Los Angeles, CA 90089, USA. FAU - Tretyakova, Natalia AU - Tretyakova N AUID- ORCID: 0000-0002-0621-6860 AD - Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA. AD - Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA. LA - eng GR - P01 CA138338/CA/NCI NIH HHS/United States GR - P30 CA077598/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - England TA - Carcinogenesis JT - Carcinogenesis JID - 8008055 RN - 0 (Butadienes) RN - 0 (Carcinogens) RN - 0 (DNA Adducts) RN - 0 (Epoxy Compounds) RN - 0 (Smoke) RN - 0 (Vehicle Emissions) RN - 478ERR5NKR (3,4-epoxy-1-butene) RN - EC 1.14.13.- (Cytochrome P-450 CYP2E1) RN - EC 1.14.14.1 (CYP2A6 protein, human) RN - EC 1.14.14.1 (Cytochrome P-450 CYP2A6) RN - EC 2.5.1.- (glutathione S-transferase T1) RN - EC 2.5.1.18 (Glutathione Transferase) RN - JSD5FGP5VD (1,3-butadiene) RN - WYQ7N0BPYC (Acetylcysteine) SB - IM MH - Acetylcysteine/urine MH - Adult MH - Aged MH - Asian/genetics MH - Butadienes/*toxicity MH - Carcinogens/metabolism/toxicity MH - Cytochrome P-450 CYP2A6/*genetics MH - Cytochrome P-450 CYP2E1/*genetics MH - DNA Adducts/*drug effects/genetics/urine MH - Epoxy Compounds/adverse effects/urine MH - Ethnicity/genetics MH - Female MH - Glutathione Transferase/genetics MH - Humans MH - Male MH - Middle Aged MH - Native Hawaiian or Other Pacific Islander/genetics MH - Smoke/adverse effects MH - Smokers MH - Spectrometry, Mass, Electrospray Ionization MH - Tobacco Products/adverse effects MH - Vehicle Emissions/toxicity MH - White People/genetics PMC - PMC8163050 EDAT- 2021/03/12 06:00 MHDA- 2021/09/30 06:00 PMCR- 2022/03/06 CRDT- 2021/03/11 06:47 PHST- 2020/11/06 00:00 [received] PHST- 2021/02/10 00:00 [revised] PHST- 2021/03/03 00:00 [accepted] PHST- 2021/03/12 06:00 [pubmed] PHST- 2021/09/30 06:00 [medline] PHST- 2021/03/11 06:47 [entrez] PHST- 2022/03/06 00:00 [pmc-release] AID - 6159930 [pii] AID - bgab020 [pii] AID - 10.1093/carcin/bgab020 [doi] PST - ppublish SO - Carcinogenesis. 2021 May 28;42(5):694-704. doi: 10.1093/carcin/bgab020.