LC-MS/MS Coupled
with a Stable-Isotope Dilution Method
for the Quantitation of Thioproline-Glycine: A Novel Metabolite in
Formaldehyde- and Oxidative Stress-Exposed Cells
Posted on 2020-07-07 - 18:40
Formaldehyde (FA)
is a human carcinogen that is ubiquitous in the
ambient environment and also generated endogenously in oxidatively
stressed cells. There is accumulated evidence that FA is an etiological
agent of leukemia development in humans. To develop a biomarker for
FA exposure, we have, in this study, developed a liquid chromatography-tandem
mass spectrometry (LC-MS/MS) coupled with stable isotope-dilution
method to explore the reactivity of FA with glutathione (GSH) in physiologically
relevant conditions. Interestingly, analysis of the reaction mixture
by LC-MS/MS revealed exposure concentration- and duration-dependent
formation of thioproline-glycine (SPro-Gly) produced by reaction of
FA with cysteinyl-glycine (Cys-Gly) as a novel metabolite. Furthermore,
dose-dependent formation of the thioproline adduct was observed in
human cells separately exposed to FA and Fe2+-EDTA, a hydroxyl
radical source. To the best of our knowledge, this is the first study
reporting a thiazolidine carboxylic acid formed by reaction of FA
and Cys-Gly is a major metabolite of FA. The results suggest a variety
of GSH-derived thiazolidine metabolites may serve as potential biomarkers
for FA and oxidative stress exposure, and the developed LC-MS/MS method
provides a means for accurate determination of SPro-Gly as a dosimeter
of oxidative stress and formaldehyde exposure.
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Pan, Guanrui; Ham, Yat-Hing; Chan, Ho Wai; Yao, Jing; Chan, Wan (2020). LC-MS/MS Coupled
with a Stable-Isotope Dilution Method
for the Quantitation of Thioproline-Glycine: A Novel Metabolite in
Formaldehyde- and Oxidative Stress-Exposed Cells. ACS Publications. Collection. https://doi.org/10.1021/acs.chemrestox.0c00170