title: Adductomic Screening of Hemoglobin Adducts and Monitoring of Micronuclei in School-Age Children.
abstract: Electrophilic compounds/metabolites present in humans, originating from endogenous processes or exogenous exposure, pose a risk to health effects through their reactions with nucleophilic sites in proteins and DNA, forming adducts. Adductomic approaches are developed to screen for adducts to biomacromolecules in vivo by mass spectrometry (MS), with the aim to detect adducts corresponding to unknown exposures from electrophiles. In the present study, adductomic screening was performed using blood samples from healthy children about 12 years old (n = 51). The frequencies of micronuclei (MN) in erythrocytes in peripheral blood were monitored as a measure of genotoxic effect/genotoxic exposure. The applied adductomic approach has been reported earlier by us and is based on analysis of N-terminal valine adducts in hemoglobin (Hb) by liquid chromatography tandem mass spectrometry (LC-MS/MS). High resolution MS was introduced for refined screening of previously unknown N-terminal Hb adducts. Measured adduct levels were compared with MN frequencies using multivariate data analysis. In the 51 individuals, a total of 24 adducts (whereof 12 were previously identified) were observed and their levels quantified. Relatively large interindividual variations in adduct levels were observed. The data analysis (with partial least-squares regression) showed that as much as 60% of the MN variation could be explained by the adduct levels. This study, for the first time, applies the combination of these sensitive methods to measure the internal dose of potentially genotoxic chemicals and genotoxic effects, respectively. The results indicate that this is a valuable approach for the characterization of exposure to chemical risk factors for the genotoxic effects present in individuals of the general population.
authors.affiliation: Department of Environmental Science and Analytical Chemistry, Stockholm University , SE-106 91 Stockholm, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Carlsson
authors.affiliation: Department of Environmental Science and Analytical Chemistry, Stockholm University , SE-106 91 Stockholm, Sweden.
authors.forename: Jenny
authors.initials: J
authors.lastname: Aasa
authors.affiliation: Swedish National Food Agency , SE-751 26 Uppsala, Sweden.
authors.forename: Natalia
authors.initials: N
authors.lastname: Kotova
authors.affiliation: Swedish National Food Agency , SE-751 26 Uppsala, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Vare
authors.affiliation: Department of Environmental Science and Analytical Chemistry, Stockholm University , SE-106 91 Stockholm, Sweden.
authors.forename: Pedro F M
authors.initials: PFM
authors.lastname: Sousa
authors.affiliation: Department of Oncology-Pathology, Karolinska Institute , SE-171 77 Stockholm, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Rydberg
authors.affiliation: Swedish National Food Agency , SE-751 26 Uppsala, Sweden.
authors.forename: Lilianne
authors.initials: L
authors.lastname: Abramsson-Zetterberg
authors.affiliation: Department of Environmental Science and Analytical Chemistry, Stockholm University , SE-106 91 Stockholm, Sweden.
authors.forename: Margareta
authors.identifier: 0000-0002-5626-1125
authors.initials: M
authors.lastname: Törnqvist
mesh_terms: D002648:Child; D002853:Chromatography, Liquid; D018736:DNA Adducts / Q000378:metabolism*; D004781:Environmental Exposure; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity; D053719:Tandem Mass Spectrometry
chemical_list: D018736:DNA Adducts; D006454:Hemoglobins; D009153:Mutagens