PMID- 21749114
OWN - NLM
STAT- MEDLINE
DCOM- 20120118
LR  - 20211020
IS  - 1520-5010 (Electronic)
IS  - 0893-228X (Print)
IS  - 0893-228X (Linking)
VI  - 24
IP  - 9
DP  - 2011 Sep 19
TI  - Quantitative analysis of trihydroxybutyl mercapturic acid, a urinary metabolite 
      of 1,3-butadiene, in humans.
PG  - 1516-26
LID - 10.1021/tx2001306 [doi]
AB  - 1,3-Butadiene (BD) is a known human carcinogen present in cigarette smoke and in 
      automobile exhaust, leading to widespread exposure of human populations. BD 
      requires cytochrome P450-mediated metabolic activation to electrophilic species, 
      e.g. 3,4-epoxy-1-butene (EB), hydroxymethyl vinyl ketone (HMVK), and 
      3,4-epoxy-1,2-diol (EBD), which form covalent adducts with DNA. EB, HMVK, and EBD 
      can be conjugated with glutathione and ultimately excreted in urine as 
      monohydroxybutenyl mercapturic acid (MHBMA), dihydroxybutyl mercapturic acid 
      (DHBMA), and trihydroxybutyl mercapturic acid (THBMA), respectively, which can 
      serve as biomarkers of BD exposure and metabolic processing. While MHBMA and 
      DHBMA have been found in smokers and nonsmokers, THBMA has not been previously 
      detected in humans. In the present work, an isotope dilution HPLC-ESI(-)-MS/MS 
      methodology was developed and employed to quantify THBMA in urine of known 
      smokers and nonsmokers (19-27 per group). The new method has excellent 
      sensitivity (LOQ, 1 ng/mL urine) and achieves accurate quantitation using a small 
      sample volume (100 muL). Mean urinary THBMA concentrations in smokers and 
      nonsmokers were found to be 21.6 and 13.7 ng/mg creatinine, respectively, 
      suggesting that there are sources of THBMA other than exposure to tobacco smoke 
      in humans, as is also the case for DHBMA. However, THBMA concentrations are 
      significantly greater in urine of smokers than that of nonsmokers (p < 0.01). 
      Furthermore, THBMA amounts in human urine declined 25-50% following smoking 
      cessation, suggesting that smoking is an important source of this metabolite in 
      humans. The HPLC-ESI(-)-MS/MS methodology developed in the present work will be 
      useful for future epidemiological studies of BD exposure and metabolism.
FAU - Kotapati, Srikanth
AU  - Kotapati S
AD  - Department of Medicinal Chemistry and the Masonic Cancer Center, University of 
      Minnesota, Minneapolis, Minnesota 55455, USA.
FAU - Matter, Brock A
AU  - Matter BA
FAU - Grant, Amy L
AU  - Grant AL
FAU - Tretyakova, Natalia Y
AU  - Tretyakova NY
LA  - eng
GR  - P01 CA138338-03/CA/NCI NIH HHS/United States
GR  - R01 CA100670-07/CA/NCI NIH HHS/United States
GR  - P01 CA138338/CA/NCI NIH HHS/United States
GR  - R01 CA100670/CA/NCI NIH HHS/United States
GR  - P30 CA077598/CA/NCI NIH HHS/United States
GR  - P01 CA138338-02/CA/NCI NIH HHS/United States
GR  - P01 CA138338-01A1/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Validation Study
DEP - 20110804
PL  - United States
TA  - Chem Res Toxicol
JT  - Chemical research in toxicology
JID - 8807448
RN  - 0 (Butadienes)
RN  - 0 (Carcinogens)
RN  - 0 (trihydroxybutyl mercapturic acid)
RN  - JSD5FGP5VD (1,3-butadiene)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/*analogs & derivatives/metabolism/urine
MH  - Butadienes/*metabolism
MH  - Carcinogens/*metabolism
MH  - Chromatography, High Pressure Liquid/methods
MH  - Humans
MH  - Sensitivity and Specificity
MH  - Smoking/metabolism/*urine
MH  - Smoking Cessation
MH  - Spectrometry, Mass, Electrospray Ionization/*methods
MH  - Tandem Mass Spectrometry/methods
PMC - PMC3208903
MID - NIHMS316607
EDAT- 2011/07/14 06:00
MHDA- 2012/01/19 06:00
PMCR- 2012/09/19
CRDT- 2011/07/14 06:00
PHST- 2011/07/14 06:00 [entrez]
PHST- 2011/07/14 06:00 [pubmed]
PHST- 2012/01/19 06:00 [medline]
PHST- 2012/09/19 00:00 [pmc-release]
AID - 10.1021/tx2001306 [doi]
PST - ppublish
SO  - Chem Res Toxicol. 2011 Sep 19;24(9):1516-26. doi: 10.1021/tx2001306. Epub 2011 
      Aug 4.