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Analysis of hemoglobin adducts from acrylamide, glycidamide and ethylene oxide in paired mother/cordblood samples from Denmark
Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Environmental Chemistry.
Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
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2011 (English)In: Chemical Research in Toxicology, ISSN 0893-228X, E-ISSN 1520-5010, Vol. 24, no 11, 1957-1965 p.Article in journal (Refereed) Published
Abstract [en]

The knowledge about fetal exposure to acrylamide/glycidamide from the maternal exposure through food is limited. Acrylamide, glycidamide, and ethylene oxide are electrophiles and form adducts with hemoglobin (Hb), which could be used for in vivo dose measurement. In this study, a method for analysis of Hb adducts by liquid chromatography–mass spectrometry, the adduct FIRE procedure, was applied to measurements of adducts from these compounds in maternal blood samples (n = 87) and umbilical cord blood samples (n = 219). The adduct levels from the three compounds, acrylamide, glycidamide, and ethylene oxide, were increased in tobacco smokers. Highly significant correlations were found between cord and maternal blood with regard to measured adduct levels of the three compounds. The mean cord/maternal hemoglobin adduct level ratios were 0.48 (range 0.27–0.86) for acrylamide, 0.38 (range 0.20–0.73) for glycidamide, and 0.43 (range 0.17–1.34) for ethylene oxide. In vitro studies with acrylamide and glycidamide showed a lower (0.38–0.48) rate of adduct formation with Hb in cord blood than with Hb in maternal blood, which is compatible with the structural differences in fetal and adult Hb. Together, these results indicate a similar life span of fetal and maternal erythrocytes. The results showed that the in vivo dose in fetal and maternal blood is about the same and that the placenta gives negligible protection of the fetus to exposure from the investigated compounds. A trend of higher levels of the measured adducts in cord blood with gestational age was observed, which may reflect the gestational age-related change of the cord blood Hb composition toward a higher content of adult Hb. The results suggest that the Hb adduct levels measured in cord blood reflect the exposure to the fetus during the third trimester. The evaluation of the new analytical method showed that it is suitable for monitoring of background exposures of the investigated electrophilic compounds in large population studies.

Place, publisher, year, edition, pages
2011. Vol. 24, no 11, 1957-1965 p.
National Category
Chemical Sciences
Research subject
Environmental Chemistry
Identifiers
URN: urn:nbn:se:su:diva-62978DOI: 10.1021/tx200284uISI: 000297082500020OAI: oai:DiVA.org:su-62978DiVA: diva2:446391
Available from: 2011-10-07 Created: 2011-10-06 Last updated: 2017-12-08Bibliographically approved
In thesis
1. Methodology for hemoglobin adduct measurement: Fetal exposures to acrylamide and other genotoxic agents
Open this publication in new window or tab >>Methodology for hemoglobin adduct measurement: Fetal exposures to acrylamide and other genotoxic agents
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

There is increasing evidence that exposure to toxic chemicals during the prenatal period constitute a higher health risk than exposure during adulthood. To characterize exposure and identify risk factors, sensitive methods for analysis of chemicals in vivo with biomarker methods are needed. Adducts to hemoglobin (Hb) have been shown useful as biomarkers of dose in blood of reactive compounds/metabolites, which are toxic due to reactions with biomacromolecules.

The aim of this thesis was to develop a new method for the analysis of Hb adducts suitable for analysis of large sample series, and then to apply the method for measurements of Hb adducts from exposure to acrylamide, glycidamide and ethylene oxide in mother/cord blood samples from five European countries.

A new method for measurements of N-terminal Hb adducts, denoted the adduct FIRE procedure, was developed using the fluorescein isothiocyanate Edman reagent. With the new procedure, optimized for LC/MS analysis, a high sensitivity and reproducibility was achieved. The new method made it possible to perform measurements of low exposures to the studied genotoxic compounds in approximately 1350 maternal and cord blood samples.

The results show that the fetus is exposed to a similar in vivo dose of the studied compounds as the mother. The measured Hb adduct levels show that acrylamide exposure from food intake is higher for the participating mothers fromUK compared to the mothers from the other countries. The measured Hb adduct levels form a basis for evaluations of relationships between exposure and health risks, and ongoing studies indicate associations between acrylamide Hb adduct levels and birth weight.

The developed method was also used for identification of an unknown Hb adduct, which was shown to originate from methyl vinyl ketone (MVK), a highly reactive and toxic compound. The identity of the adduct was confirmed with synthesized standards. There exist both natural and anthropogenic sources to MVK, and to what extent the MVK-adduct reflects exogenous exposure is yet not clarified.

Place, publisher, year, edition, pages
Stockholm: Department of Materials and Environmental Chemistry (MMK), Stockholm University, 2011. 54 p.
National Category
Chemical Sciences
Research subject
Environmental Chemistry
Identifiers
urn:nbn:se:su:diva-63026 (URN)978-91-7447-376-6 (ISBN)
Public defence
2011-11-11, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (Swedish)
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Note
At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 3: Epub ahead of print.Available from: 2011-10-20 Created: 2011-10-07 Last updated: 2011-10-10Bibliographically approved

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