PMID- 38315500
OWN - NLM
STAT- MEDLINE
DCOM- 20240220
LR  - 20240325
IS  - 1520-5010 (Electronic)
IS  - 0893-228X (Linking)
VI  - 37
IP  - 2
DP  - 2024 Feb 19
TI  - Association of Urinary N7-(1-hydroxyl-3-buten-1-yl) Guanine (EB-GII) Adducts and 
      Butadiene-Mercapturic Acids with Lung Cancer Development in Cigarette Smokers.
PG  - 374-384
LID - 10.1021/acs.chemrestox.3c00336 [doi]
AB  - Approximately 10% of smokers will develop lung cancer. Sensitive predictive 
      biomarkers are needed to identify susceptible individuals. 1,3-Butadiene (BD) is 
      among the most abundant tobacco smoke carcinogens. BD is metabolically activated 
      to 3,4-epoxy-1-butene (EB), which is detoxified via the glutathione 
      conjugation/mercapturic acid pathway to form monohydroxybutenyl mercapturic acid 
      (MHBMA) and dihydroxybutyl mercapturic acid (DHBMA). Alternatively, EB can react 
      with guanine nucleobases of DNA to form N7-(1-hydroxyl-3-buten-1-yl) guanine 
      (EB-GII) adducts. We employed isotope dilution LC/ESI-HRMS/MS methodologies to 
      quantify MHBMA, DHBMA, and EB-GII in urine of smokers who developed lung cancer 
      (N = 260) and matched smoking controls (N = 259) from the Southern Community 
      Cohort (white and African American). The concentrations of all three biomarkers 
      were significantly higher in smokers that subsequently developed lung cancer as 
      compared to matched smoker controls after adjusting for age, sex, and 
      race/ethnicity (p < 0.0001 for EB-GII, p < 0.0001 for MHBMA, and p = 0.0007 for 
      DHBMA). The odds ratio (OR) for lung cancer development was 1.63 for MHBMA, 1.37 
      for DHBMA, and 1.97 for EB-GII, with a higher OR in African American subjects 
      than in whites. The association of urinary EB-GII, MHBMA, and DHBMA with lung 
      cancer status did not remain upon adjustment for total nicotine equivalents. 
      These findings reveal that urinary MHBMA, DHBMA, and EB-GII are directly 
      correlated with the BD dose delivered via smoking and are associated with lung 
      cancer risk.
FAU - Jokipii Krueger, Caitlin C
AU  - Jokipii Krueger CC
AUID- ORCID: 0000-0002-5072-6614
AD  - Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, 
      United States.
AD  - Department of Medicinal Chemistry, University of Minnesota, Minneapolis, 
      Minnesota 55455, United States.
FAU - Park, Sungshim L
AU  - Park SL
AD  - Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii 96822, 
      United States.
FAU - Patel, Yesha
AU  - Patel Y
AD  - Department of Preventative Medicine, School of Medicine, University of Southern 
      California, Los Angeles, California 90089, United States.
FAU - Stram, Daniel O
AU  - Stram DO
AD  - Department of Preventative Medicine, School of Medicine, University of Southern 
      California, Los Angeles, California 90089, United States.
FAU - Aldrich, Melinda
AU  - Aldrich M
AD  - Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer 
      Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, 
      United States.
FAU - Cai, Qiuyin
AU  - Cai Q
AD  - Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer 
      Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, 
      United States.
FAU - Tretyakova, Natalia Y
AU  - Tretyakova NY
AUID- ORCID: 0000-0002-0621-6860
AD  - Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, 
      United States.
AD  - Department of Medicinal Chemistry, University of Minnesota, Minneapolis, 
      Minnesota 55455, United States.
LA  - eng
GR  - P01 CA138338/CA/NCI NIH HHS/United States
GR  - U01 CA202979/CA/NCI NIH HHS/United States
GR  - P30 CA068485/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20240205
PL  - United States
TA  - Chem Res Toxicol
JT  - Chemical research in toxicology
JID - 8807448
RN  - JSD5FGP5VD (1,3-butadiene)
RN  - 0 (Butadienes)
RN  - WYQ7N0BPYC (Acetylcysteine)
RN  - 5Z93L87A1R (Guanine)
RN  - 0 (Biomarkers)
RN  - 0 (DNA Adducts)
SB  - IM
MH  - Humans
MH  - Smokers
MH  - Butadienes/metabolism
MH  - Acetylcysteine/metabolism
MH  - *Lung Neoplasms/chemically induced
MH  - Guanine
MH  - Biomarkers/urine
MH  - *Tobacco Products
MH  - DNA Adducts
EDAT- 2024/02/05 14:44
MHDA- 2024/02/20 11:50
CRDT- 2024/02/05 11:43
PHST- 2024/02/20 11:50 [medline]
PHST- 2024/02/05 14:44 [pubmed]
PHST- 2024/02/05 11:43 [entrez]
AID - 10.1021/acs.chemrestox.3c00336 [doi]
PST - ppublish
SO  - Chem Res Toxicol. 2024 Feb 19;37(2):374-384. doi: 10.1021/acs.chemrestox.3c00336. 
      Epub 2024 Feb 5.