Relationships between airborne pollutants, serum albumin adducts and short-term health outcomes in an experimental crossover study

Preston, George W.; Dagnino, Sonia; Ponzi, Erica; Sozeri, Osman; Veldhoven, Karin van; Barratt, Benjamin; Liu, Sa; Grigoryan, Hasmik; Lu, Sixin Samantha; Rappaport, Stephen M.; Chung, Kian Fan; Cullinan, Paul; Sinharay, Rudy; Kelly, Frank J.; Chadeau‐Hyam, Marc; Víneis, Paolo; Phillips, David H.

doi:10.1016/j.chemosphere.2019.124667

Cited by 8 publications

(9 citation statements)

References 24 publications

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“…The interpretation of the massive data appear to be too complicated (Carlsson et al 2019 ). In addition, especially, for the analyses of albumin adducts, trypsin digestion yields large peptide fragments that cannot be analyzed with sufficient sensitivity (Preston et al 2017 ). The method should be first tested with synthetic standards that have been characterized according to the standard protocols of organic chemistry.…”

Section: Discussionmentioning

confidence: 99%

“…Proteases, such as trypsin, can produce long peptides such as the T3-tryptic peptide A 21 LVLIAFAQYLQQCPFEDHVK 41 , whereas pronase digestion yields mono- di- or tripeptide Cys-containing adducts. The T3 peptide was used in most recent studies for a targeted and untargeted biomonitoring approach (Li et al 2011 ; Preston et al 2020 ). Combination of enzymes yields different lengths of peptides (Table 2 ).…”

Section: Protein Adductsmentioning

confidence: 99%

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Quo vadis blood protein adductomics?

Sabbioni

Day²

2021

Arch Toxicol

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Chemicals are measured regularly in air, food, the environment, and the workplace. Biomonitoring of chemicals in biological fluids is a tool to determine the individual exposure. Blood protein adducts of xenobiotics are a marker of both exposure and the biologically effective dose. Urinary metabolites and blood metabolites are short term exposure markers. Stable hemoglobin adducts are exposure markers of up to 120 days. Blood protein adducts are formed with many xenobiotics at different sites of the blood proteins. Newer methods apply the techniques developed in the field of proteomics. Larger adducted peptides with 20 amino acids are used for quantitation. Unfortunately, at present the methods do not reach the limits of detection obtained with the methods looking at single amino acid adducts or at chemically cleaved adducts. Therefore, to progress in the field new approaches are needed.

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Section: Discussionmentioning

confidence: 99%

Section: Protein Adductsmentioning

confidence: 99%

Quo vadis blood protein adductomics?

Sabbioni

Day²

2021

Arch Toxicol

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“…In the second study, Preston et al [80] examined a larger number of Oxford Street II samples by the FS-SRM method. Associations between amounts of putative adducts and two types of measure were tested: Pollution (e.g., ambient concentrations of nitrogen dioxide and particulate matter) and health outcome (e.g., measures of lung health and arterial stiffness).…”

Section: Human Biomonitoringmentioning

confidence: 99%

Protein Adductomics: Analytical Developments and Applications in Human Biomonitoring

Preston

Phillips

2019

Toxics

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Proteins contain many sites that are subject to modification by electrophiles. Detection and characterisation of these modifications can give insights into environmental agents and endogenous processes that may be contributing factors to chronic human diseases. An untargeted approach, utilising mass spectrometry to detect modified amino acids or peptides, has been applied to blood proteins haemoglobin and albumin, focusing in particular on the N-terminal valine residue of haemoglobin and the cysteine-34 residue in albumin. Technical developments to firstly detect simultaneously multiple adducts at these sites and then subsequently to identify them are reviewed here. Recent studies in which the methods have been applied to biomonitoring human exposure to environmental toxicants are described. With advances in sensitivity, high-throughput handling of samples and robust quality control, these methods have considerable potential for identifying causes of human chronic disease and of identifying individuals at risk.

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“… 28 This method has been applied in a number of studies including a study on urban ambient air pollution that reported association of adducts with air pollutants, as well as of adducts with health outcome measures. 29 In another study of occupational exposure to benzene, a positive association was found for putative benzene metabolite adducts. 30 Furthermore, the Cys34 method has been applied in studies of lung cancer 31 and childhood leukemia.…”

Section: Introductionmentioning

confidence: 97%

“…The adduct annotation is aided by software interrogation of tandem mass spectra based on retention time, accurate mass, elemental composition, and using comparison with databases . This method has been applied in a number of studies including a study on urban ambient air pollution that reported association of adducts with air pollutants, as well as of adducts with health outcome measures . In another study of occupational exposure to benzene, a positive association was found for putative benzene metabolite adducts .…”

Section: Introductionmentioning

confidence: 99%

Pathways to Identify Electrophiles In Vivo Using Hemoglobin Adducts: Hydroxypropanoic Acid Valine Adduct and Its Possible Precursors

Vryonidis

Karlsson

Aasa

et al. 2022

Chem. Res. Toxicol.

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Analytical methods and tools for the characterization of the human exposome by untargeted mass spectrometry approaches are advancing rapidly. Adductomics methods have been developed for untargeted screening of short-lived electrophiles, in the form of adducts to proteins or DNA, in vivo. The identification of an adduct and its precursor electrophile in the blood is more complex than that of stable chemicals. The present work aims to illustrate procedures for the identification of an adduct to N-terminal valine in hemoglobin detected with adductomics, and pathways for the tracing of its precursor and possible exposure sources. Identification of the adduct proceeded via preparation and characterization of standards of adduct analytes. Possible precursor(s) and exposure sources were investigated by measurements in blood of adduct formation by precursors in vitro and adduct levels in vivo. The adduct was identified as hydroxypropanoic acid valine (HPA-Val) by verification with a synthesized reference. The HPA-Val was measured together with other adducts (from acrylamide, glycidamide, glycidol, and acrylic acid) in human blood (n = 51, schoolchildren). The HPA-Val levels ranged between 6 and 76 pmol/g hemoglobin. The analysis of reference samples from humans and rodents showed that the HPA-Val adduct was observed in all studied samples. No correlation of the HPA-Val level with the other studied adducts was observed in humans, nor was an increase in tobacco smokers observed. A small increase was observed in rodents exposed to glycidol. The formation of the HPA-Val adduct upon incubation of blood with glycidic acid (an epoxide) was shown. The relatively high adduct levels observed in vivo in relation to the measured reactivity of the epoxide, and the fact that the epoxide is not described as naturally occurring, suggest that glycidic acid is not the only precursor of the HPA-Val adduct identified in vivo. Another endogenous electrophile is suspected to contribute to the in vivo HPA-Val adduct level.

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Relationships between airborne pollutants, serum albumin adducts and short-term health outcomes in an experimental crossover study

Cited by 8 publications

References 24 publications

Quo vadis blood protein adductomics?

Quo vadis blood protein adductomics?

Protein Adductomics: Analytical Developments and Applications in Human Biomonitoring

Pathways to Identify Electrophiles In Vivo Using Hemoglobin Adducts: Hydroxypropanoic Acid Valine Adduct and Its Possible Precursors

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