Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Detection of Benzo[a]pyrene Diol Epoxide Adducts to Histidine and Lysine in Serum Albumin In Vivo by High-Resolution-Tandem Mass Spectrometry
Δημιουργός/Συγγραφέας:	Zurita, Javier Motwani, Hitesh V Ilag, Leopold L [EL] Σουλιώτης, Βασίλης Λ.[EN] Souliotis, Vassilis L. [EL] Κυρτόπουλος, Σωτήριος Α.[EN] Kyrtopoulos, Soterios A. Nilsson, Ulrika Törnqvist, Margareta
Ημερομηνία:	2022-01-08
Γλώσσα:	Αγγλικά
ISSN:	2305-6304
DOI:	10.3390/toxics10010027
Άλλο:	35051069
Περίληψη:	Electrophilic diol epoxide metabolites are involved in the carcinogenicity of benzo[a]pyrene, one of the widely studied polycyclic aromatic hydrocarbons (PAHs). The exposure of humans to this PAH can be assessed by measuring stable blood protein adducts, such as to histidine and lysine in serum albumin, from their reactive metabolites. In this respect, measurement of the adducts originating from the genotoxic (+)-anti-benzo[a]pyrene diol epoxide is of interest. However, these are difficult to measure at such low levels as are expected in humans generally exposed to benzo[a]pyrene from air pollution and the diet. The analytical methods detecting PAH-biomarkers still suffer from low selectivity and/or detectability to enable generation of data for calculation of in vivo doses of specific stereoisomers, for evaluation of risk factors and assessing risk from exposures to PAH. Here, we suggest an analytical methodology based on high-pressure liquid chromatography (HPLC) coupled to high-resolution tandem mass spectrometry (MS) to lower the detection limits as well as to increase the selectivity with improvements in both chromatographic separation and mass determination. Method development was performed using serum albumin alkylated in vitro by benzo[a]pyrene diol epoxide isomers. The (+)-anti-benzo[a]pyrene diol epoxide adducts could be chromatographically resolved by using an HPLC column with a pentafluorophenyl stationary phase. Interferences were further diminished by the high mass accuracy and resolving power of Orbitrap MS. The achieved method detection limit for the (+)-anti-benzo[a]pyrene diol epoxide adduct to histidine was approximately 4 amol/mg serum albumin. This adduct as well as the adducts to histidine from (-)-anti- and (+/-)-syn-benzo[a]pyrene diol epoxide were quantified in the samples from benzo[a]pyrene-exposed mice. Corresponding adducts to lysine were also quantified. In human serum albumin, the anti-benzo[a]pyrene diol epoxide adducts to histidine were detected in only two out of twelve samples and at a level of approximately 0.1 fmol/mg.
Τίτλος πηγής δημοσίευσης:	Toxics
Τόμος/Κεφάλαιο:	10
Τεύχος:	1
Θεματική Κατηγορία:	[EL] Χημική Βιολογία[EN] Chemical Biology [EL] Βιοχημεία[EN] Biochemistry [EL] Αναλυτική χημεία[EN] Analytical chemistry [EL] Φασματοσκοπία[EN] Spectroscopy
Λέξεις-Κλειδιά:	Human exposure Liquid chromatography-mass spectrometry (LC-MS/MS) Metabolism Polycyclic aromatic hydrocarbons Protein adducts
EU Grant:	AMBIPAH (Programme Quality of Life and management of living resources)
EU Grant identifier:	QLK4-CT-2002-02402 2016-02170 2019-2020
Κάτοχος πνευματικών δικαιωμάτων:	© 2022 by the authors. Licensee MDPI, Basel, Switzerland
Όροι και προϋποθέσεις δικαιωμάτων:	This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://www.mdpi.com/2305-6304/10/1/27
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο