2 research outputs found
Comparative Cytotoxicity of Six Iodinated Disinfection Byproducts on Nontransformed Epithelial Human Colon Cells
Exposure
to disinfection byproducts (DBPs) in chlorinated drinking
water has been positively associated with increased risk of colon,
bladder, and rectum cancers. Iodinated DBPs (I-DBPs) are of concern
as this class exhibits enhanced cytotoxicity and genotoxicity compared
to those of chlorinated and brominated equivalents in Chinese hamster
ovary (CHO) cells. We tested the impact of six I-DBPs on immortalized
normal human colon epithelial cells (CCD 841 CoN). Our assay showed
the following rank order of cytotoxicity of the I-DBPs: iodoacetic
acid (IAA) > iodoacetamide (IAcAm) > bromoiodoacetamide (BIAcAm)
>
chloroiodoacetamide (CIAcAm) > bromoiodoacetic acid (BIAA) ≈
diiodoacetic acid (DIAA). The enhanced cytotoxicity of IAA compared
with those of other haloacetic acids agrees with studies conducted
on CHO cells. IAcAm was found to be 3.5 times more cytotoxic than
BIAcAm and 9.4 times more cytotoxic than CIAcAm. The cytotoxicity
of both dihaloacids (i.e., BIAA and DIAA) was <1% of that of the
monohaloacid IAA. Apart from IAA, the nitrogenous I-DBPs demonstrated
cytotoxicity greater than that of the carbonaceous I-DBPs. The results
are consistent with previous CHO studies of dihalogenated I-DBPs but
not monohalogenated ones. This study has implications for drinking
water management strategies aimed at minimizing the formation of I-DBPs
associated with enhanced cytotoxicity
Expanding Per- and Polyfluoroalkyl Substances Coverage in Nontargeted Analysis Using Data-Independent Analysis and IonDecon
Per- and polyfluoroalkyl substances (PFAS) are widespread,
persistent
environmental contaminants that have been linked to various health
issues. Comprehensive PFAS analysis often relies on ultra-high-performance
liquid chromatography coupled with high-resolution mass spectrometry
(UHPLC HRMS) and molecular fragmentation (MS/MS). However, the selection
and fragmentation of ions for MS/MS analysis using data-dependent
analysis results in only the topmost abundant ions being selected.
To overcome these limitations, All Ions fragmentation (AIF) can be
used alongside data-dependent analysis. In AIF, ions across the entire m/z range are simultaneously fragmented;
hence, precursor–fragment relationships are lost, leading to
a high false positive rate. We introduce IonDecon, which filters All
Ions data to only those fragments correlating with precursor ions.
This software can be used to deconvolute any All Ions files and generates
an open source DDA formatted file, which can be used in any downstream
nontargeted analysis workflow. In a neat solution, annotation of PFAS
standards using IonDecon and All Ions had the exact same false positive
rate as when using DDA; this suggests accurate annotation using All
Ions and IonDecon. Furthermore, deconvoluted All Ions spectra retained
the most abundant peaks also observed in DDA, while filtering out
much of the artifact peaks. In complex samples, incorporating AIF
and IonDecon into workflows can enhance the MS/MS coverage of PFAS
(more than tripling the number of annotations in domestic sewage).
Deconvolution in complex samples of All Ions data using IonDecon did
retain some false fragments (fragments not observed when using ion
selection, which were not isotopes or multimers), and therefore DDA
and intelligent acquisition methods should still be acquired when
possible alongside All Ions to decrease the false positive rate. Increased
coverage of PFAS can inform on the development of regulations to address
the entire PFAS problem, including both legacy and newly discovered
PFAS