A novel method for source-specific hemoglobin adducts of nitro-polycyclic aromatic hydrocarbons

Abstract

Polycyclic aromatic hydrocarbons (PAH) are ubiquitous air pollutants associated with negative impacts on growth, development and behavior in children. Source-specific biological markers of PAH exposure are needed for targeting interventions to protect children. Nitro-derivatives of PAH can act as markers of exposure to diesel exhaust, gasoline exhaust, or general combustion sources. Using a novel HPLC-APCI-MS/MS detection method, we examined four hemoglobin (Hb) adducts of nitro-PAH metabolites and the Hb adduct of a benzo[a]pyrene (BaP) metabolite in 22 umbilical cord blood samples. The samples were collected from a birth cohort with comprehensive data on prenatal PAH exposure, including prenatal personal air monitoring and DNA adducts in maternal and umbilical cord blood. Using non-parametric analyses, heat maps, and principal component analysis (PCA), we analyzed the relationship between the five Hb adducts and previous PAH measurements, with each measurement representing a different duration of exposure. We found that Hb adducts derived from several diesel-related nitro-PAHs (2-nitrofluorene and 1-nitropyrene) were significantly correlated (r = 0.77, p ≤ 0.0001) and grouped together in PCA. Nitro-PAH derived Hb adducts were largely unrelated to previously collected measures of exposure to a number of PAH parent compounds. These measures need to be validated in a larger sample.

Nitrated Polycyclic Aromatic Hydrocarbons and Arachidonic Acid Metabolisms Relevant to Cardiovascular Pathophysiology: Findings from a Panel Study in Healthy Adults

“…People can be exposed to nitro-PAHs from different sources. , For example, it has been reported that 1-nitronaphthalene and 2-nitronaphthalene are largely produced through smoking, while 1-nitropyrene, 2-nitrofluorene, and 9-nitrophenanthrene are mainly found in diesel exhaust. − In this study, 1-AP has a particularly strong association with 20-HETE, 11-dhTXB 2 , 8-OHdG, and aMT6s. In addition, 1-AN and 2-AN are significantly associated with 20-HETE, 8-OHdG, and aMT6s.…”

Quo vadis blood protein adductomics?

“…In contrast, the hemoglobin adduct levels found in rats of bicyclic and bifunctional arylamines such as 4,4'-methylenedianiline, 4,4'-methylenebis(2-chloroaniline), 4,4'-oxydianiline, 4,4'-thiodianiline, 3,3'-dichlorobenzidine and benzidine correlate with the carcinogenic potency (Sabbioni and Schutze 1998). Roughly, the mutagenic and carcinogenic potency of arylamines is associated s (Xu et al 2014) HETE-Val, CAS:190187-17-8 t (Boysen et al 2019) CAS:2416700-26-8, main product u (Wheelock et al 2018) v (Schutze et al 1995) w (Padros and to the relative stability of the nitrenium ion, but not necessarily to the hydrolyzable hemoglobin (sulfinamide) adduct levels (Sabbioni and Sepai 1995;Sabbioni and Wild 1992) (Fig. 1S).…”

“… APCI=atmospheric pressure chemical ionization, FITC = fluorescein isothiocyanate, FLD=fluorescence detection, HBFA = heptafluorobutyric anhydride, HRMS=high resolution mass spectrometry, hydr = hydrolysis, NCI=negative chemical ionization, PFPITC = pentafluorophenyl isothiocyanate, PITC = phenylisothiocyanate a Hb b globin c (Gries and Leng 2013 ) CAS:264285-90-7 d (Sachse et al 2017 ) CAS:1531625-56-5 e (Hielscher et al 2017 ) CAS:133278-70-3; e1) (Müller 2013 ) f (von Stedingk et al 2010 ) CAS:252663-74-4; f1) (Yang et al 2018 ); f2) (Schettgen et al 2016 ) g (Yang et al 2018 ) CAS:21768-51-4 h CAS:51078-53-6 i CAS:51078-49-0 j (Carlsson et al 2015 ), only the FITC derivative has a CAS number k (Lewalter et al 2012 ) CAS:15363-84-5 l (Bader et al 2013 ) CAS:223443-77-4 m (von Stedingk et al 2014 ), N -[2-(2-oxo-3-oxazolidinyl)ethyl]-L-valine CAS:173962-82-8 n (CDC-NHANES 2020 ) N-terminal peptide (VHLTPEEK) of the ß-Hb-chain: N-(Hydroxymethyl)-VHLTPEEK (CAS:1307263-38-2), also the terminal amino acids of the α-Hb-chain was reported but not quantified in the CDC-NHANES studies, N-(hydroxymethyl)-VLSPADK, CAS:1307263-39-3; n1) (Yang et al 2017 ) o (Charneira et al 2012 ) CAS:1350434-49-9 p (Käfferlein et al 2016 ) CAS:74310-99-9 q CAS:848640-59-5 r (Mráz et al 2006 ) CAS:84860-36-6 s (Xu et al 2014 ) HETE-Val, CAS:190187-17-8 t (Boysen et al 2019 ) CAS:2416700-26-8, main product u (Wheelock et al 2018 ) v (Schutze et al 1995 ) w (Padros and Pelletier 2001 ); * were validated in the German Working Group “Analyses in Biological Materials of the permanent Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work” and the standard operation values are available online ( https://onlinelibrary.wiley.com/doi/book/10.1002/3527600418 ) ** the compounds are commercially available, SciFinder search 23.7.21 …”

“…A new, sensitive method using LC–MS/MS was published for the analysis of hemoglobin adducts of polycyclic aromatic amines deriving from nitro-polyaromatic hydrocarbons present in polluted air (Wheelock et al 2018 ). A novel method for source-specific hemoglobin adducts of nitro-polycyclic aromatic hydrocarbons was also described (Vimercati et al 2020 ).…”