A new modified Edman procedure for analysis of N-terminal valine adducts in hemoglobin by LC–MS/MS

Stedingk, Hans von; Rydberg, Per; Törnqvist, Margareta

doi:10.1016/j.jchromb.2010.03.034

Cited by 57 publications

(94 citation statements)

References 20 publications

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“…Erythrocytes were separated by centrifugation and stored at –20°C before and after shipment on dry ice. Hb adducts from acrylamide and glycidamide were simultaneously determined by the “adduct FIRE procedure” (fluorescein isothiocyanate R Edman) in 1,101 cord blood samples and 172 maternal blood samples (von Stedingk et al 2010, 2011). In brief, adducted N-terminal valines were detached using the Edman reagent fluoresceine-5-isothiocyanate.…”

Section: Methodsmentioning

confidence: 99%

Birth Weight, Head Circumference, and Prenatal Exposure to Acrylamide from Maternal Diet: The European Prospective Mother–Child Study (NewGeneris)

Pedersen

Stedingk

Botsivali

et al. 2012

Environ Health Perspect

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101

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Background: Acrylamide is a common dietary exposure that crosses the human placenta. It is classified as a probable human carcinogen, and developmental toxicity has been observed in rodents.Objectives: We examined the associations between prenatal exposure to acrylamide and birth outcomes in a prospective European mother–child study.Methods: Hemoglobin (Hb) adducts of acrylamide and its metabolite glycidamide were measured in cord blood (reflecting cumulated exposure in the last months of pregnancy) from 1,101 singleton pregnant women recruited in Denmark, England, Greece, Norway, and Spain during 2006–2010. Maternal diet was estimated through food-frequency questionnaires.Results: Both acrylamide and glycidamide Hb adducts were associated with a statistically significant reduction in birth weight and head circumference. The estimated difference in birth weight for infants in the highest versus lowest quartile of acrylamide Hb adduct levels after adjusting for gestational age and country was –132 g (95% CI: –207, –56); the corresponding difference for head circumference was –0.33 cm (95% CI: –0.61, –0.06). Findings were similar in infants of nonsmokers, were consistent across countries, and remained after adjustment for factors associated with reduced birth weight. Maternal consumption of foods rich in acrylamide, such as fried potatoes, was associated with cord blood acrylamide adduct levels and with reduced birth weight.Conclusions: Dietary exposure to acrylamide was associated with reduced birth weight and head circumference. Consumption of specific foods during pregnancy was associated with higher acrylamide exposure in utero. If confirmed, these findings suggest that dietary intake of acrylamide should be reduced among pregnant women.

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Section: Methodsmentioning

confidence: 99%

Birth Weight, Head Circumference, and Prenatal Exposure to Acrylamide from Maternal Diet: The European Prospective Mother–Child Study (NewGeneris)

Pedersen

Stedingk

Botsivali

et al. 2012

Environ Health Perspect

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101

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“…Red blood cells were isolated and stored at À20 C until further processing. Adduct levels to N-terminal valines in Hb were measured in a total of 84 samples applying the "adduct FIRE procedure" using liquid chromatographytandem mass spectrometry (LC-MS/MS; Shimadzu Prominence, AB SCIEX 3200 qtrap) for final detection (20). Method performance parameters and its application to measurements of acrylamide and glycidamide Hbadducts in cord blood samples has previously been described (20,27).…”

Section: Internal Measurements Of Pollutantsmentioning

confidence: 99%

“…This Hb-bound acrylamide represents a wellaccepted measure of internal dose and was, as well as the Hb-bound glycidamide, used as a biomarker of exposure to acrylamide in the present study. A recently developed liquid chromatography-tandem mass spectrometry method was used for measurement of the Hb adducts (20).…”

Section: Introductionmentioning

confidence: 99%

Global Gene Expression Analysis in Cord Blood Reveals Gender-Specific Differences in Response to Carcinogenic Exposure In Utero

Hochstenbach

Leeuwen

Gmuender

et al. 2012

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: It has been suggested that fetal carcinogenic exposure might lead to predisposition to develop cancer during childhood or in later life possibly through modulation of the fetal transcriptome. Because gender effects in the incidence of childhood cancers have been described, we hypothesized differences at the transcriptomic level in cord blood between male and female newborns as a consequence of fetal carcinogenic exposure. The objective was to investigate whether transcriptomic responses to dietary genotoxic and nongenotoxic carcinogens show gender-specific mechanisms-of-action relevant for chemical carcinogenesis.Methods: Global gene expression was applied in umbilical cord blood samples, the CALUX-assay was used for measuring dioxin(-like), androgen(-like), and estrogen(-like) internal exposure, and acrylamide-hemoglobin adduct levels were determined by mass spectrometry adduct-FIRE-procedure TM . To link gene

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“…Further modifications of the Edman procedure for analysis of N-terminal valine adducts seem promising for future adduct profiling studies (Von Stedingk H. et al 2010; Von Stedingk H. et al 2011). These new approaches are aimed to establish a tool for multi-adduct profiling of reactive, and potentially genotoxic, compounds in mixtures.…”

Section: Introductionmentioning

confidence: 99%

Exposure profiling of reactive compounds in complex mixtures

et al. 2013

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Humans are constantly exposed to mixtures, such as tobacco smoke, exhaust from diesel, gasoline or new bio-fuels, containing several thousand compounds, including many known human carcinogens. Covalent binding of reactive compounds or their metabolites to DNA and formation of stable adducts is believed to be the causal link between exposure and carcinogenesis. DNA and protein adducts are well established biomarkers for the internal dose of reactive compounds or their metabolites and are an integral part of science-based risk assessment. However, technical limitations have prevented comprehensive detection of a broad spectrum of adducts simultaneously. Therefore, most studies have focused on measurement of abundant individual adducts. These studies have produced valuable insight into the metabolism of individual carcinogens, but they are insufficient for risk assessment of exposure to complex mixtures. To overcome this limitation, we present herein proof-of-principle for comprehensive exposure assessment, using N-terminal valine adduct profiles as a biomarker. The reported method is based on our previously established immunoaffinity liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with modification to enrich all N-terminal valine alkylated peptides. The method was evaluated using alkylated peptide standards and globin reacted in vitro with alkylating agents (1,2-epoxy-3-butene, 1,2:3,4-diepoxybutane, propylene oxide, styrene oxide, N-ethyl-N-nitrosourea and methyl methanesulfonate), known to form N-terminal valine adducts. To demonstrate proof-of-principle, the method was successfully applied to globin from mice treated with four model compounds. The results suggest that this novel approach might be suitable for in vivo biomonitoring.

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A new modified Edman procedure for analysis of N-terminal valine adducts in hemoglobin by LC–MS/MS

Cited by 57 publications

References 20 publications

Birth Weight, Head Circumference, and Prenatal Exposure to Acrylamide from Maternal Diet: The European Prospective Mother–Child Study (NewGeneris)

Birth Weight, Head Circumference, and Prenatal Exposure to Acrylamide from Maternal Diet: The European Prospective Mother–Child Study (NewGeneris)

Global Gene Expression Analysis in Cord Blood Reveals Gender-Specific Differences in Response to Carcinogenic Exposure In Utero

Exposure profiling of reactive compounds in complex mixtures

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