Analysis of Hemoglobin Adducts from Acrylamide, Glycidamide, and Ethylene Oxide in Paired Mother/Cord Blood Samples from Denmark

Stedingk, Hans von; Vikström, Anna; Rydberg, Per; Pedersen, Marie; Nielsen, Jeanette K.; Segerbäck, Dan; Knudsen, Lisbeth E.; Törnqvist, Margareta

doi:10.1021/tx200284u

Cited by 82 publications

(69 citation statements)

References 56 publications

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“…Furthermore, in vitro studies showed that rates of adduct formation are lower in the cord blood probably because of structural differences between fetal and adult Hb. The authors therefore conclude that the fetus is exposed to the same AA and GA doses as the mother (von Stedingk et al, 2011).…”

Section: Developmental Consequencesmentioning

confidence: 89%

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Scientific Opinion on acrylamide in food

Publication¹

2015

EFS2

342

170

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EFSA was asked to deliver a scientific opinion on acrylamide (AA) in food. AA has widespread uses as an industrial chemical. It is also formed when certain foods are prepared at temperatures above 120 °C and low moisture, especially in foods containing asparagine and reducing sugars. The CONTAM Panel evaluated 43 419 analytical results from food commodities. AA was found at the highest levels in solid coffee substitutes and coffee, and in potato fried products. Mean and 95th percentile dietary AA exposures across surveys and age groups were estimated at 0.4 to 1.9 µg/kg body weight (b.w.) per day and 0.6 to 3.4 µg/kg b.w. per day, respectively. The main contributor to total dietary exposure was generally the category 'Potato fried products (except potato crisps and snacks)'. Preferences in home-cooking can have a substantial impact on human dietary AA exposure. Upon oral intake, AA is absorbed from the gastrointestinal tract and distributed to all organs. AA is extensively metabolised, mostly by conjugation with glutathione but also by epoxidation to glycidamide (GA). Formation of GA is considered to represent the route underlying the genotoxicity and carcinogenicity of AA. Neurotoxicity, adverse effects on male reproduction, developmental toxicity and carcinogenicity were identified as possible critical endpoints for AA toxicity from experimental animal studies. The data from human studies were inadequate for dose-response assessment. The CONTAM Panel selected BMDL 10 values of 0.43 mg/kg b.w. per day for peripheral neuropathy in rats and of 0.17 mg/kg b.w. per day for neoplastic effects in mice. The Panel concluded that the current levels of dietary exposure to AA are not of concern with respect to non-neoplastic effects. However, although the epidemiological associations have not demonstrated AA to be a human carcinogen, the margins of exposure (MOEs) indicate a concern for neoplastic effects based on animal evidence. © European Food SUMMARYFollowing a request from the European Commission, the Panel on Contaminants in the Food Chain (CONTAM Panel) was asked to deliver a scientific opinion on acrylamide (AA) in food. The Panel developed the draft scientific opinion which underwent a public consultation from 1 July 2014 to 15 September 2014. The comments received and how they were taken into account when finalising the scientific opinion were published in an EFSA Technical Report (EFSA, 2015).AA is a low molecular weight, highly water soluble, organic compound. It is used inter alia as an industrial chemical and in the production of polyacrylamides. Heightened concerns about exposure to AA arose in 2002 when it was discovered that it forms when certain foods are prepared at temperatures usually above 120 °C and low moisture. It forms, at least in part, due to a Maillard reaction between certain amino acids, such as asparagine, and reducing sugars. However, several other pathways and precursors have also been proposed to contribute to AA formation. AA forms in numerous baked or fried carbohydrate-rich f...

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Section: Developmental Consequencesmentioning

confidence: 89%

“…In a Danish study, Hb-AA and Hb-GA adduct levels were measured in 87 maternal blood and 219 cord blood samples (von Stedingk et al, 2011). The correlation between cord and maternal blood were 0.69 (p for trend < 0.001) and 0.78 (p for trend < 0.001) for AA and GA, respectively.…”

Section: Developmental Consequencesmentioning

confidence: 99%

Scientific Opinion on acrylamide in food

Publication¹

2015

EFS2

342

170

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“…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%

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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“…A certain number of analytical techniques are nowadays applied in the proteic adduct analysis (26,50), as chemical and enzymatic digestions, electrophoresis or capillary liquid chromatography with different detection techniques, such as mass spectrometry and fluorescence, or immunochemical approaches, as enzymelinked immunosorbent assay (ELISA). The advancement in the instrumental performances allows high sensitivity levels, from 0.1 to 500 fmol of proteic adduct; nevertheless, there are no reports concerning the costs and time of the unavoidable purification procedure of the biological sample and the selective enrichment of the macromolecular adduct under study with respect to the unmodified proteic fraction.…”

Section: Discussionmentioning

confidence: 99%

“…In fact, protein adducts are considered a valid surrogate for DNA adducts formation, since many chemical carcinogens bind to both DNA and protein in blood with similar dose-response kinetics (3,9,11,15,16). Hemoglobin (Hb) adducts, in particular, have been found to be suitable biomarkers for evaluating exposure to toxicants (16,(17)(18)(19)(20)(21)(22)(23)(24)(25)(26), due to the fact that hemoglobin is easy to sample, forms stable adducts, which are not subject to repair processes, and has a long life time (approx. 120 days in humans).…”

Section: Introductionmentioning

confidence: 99%

New perspectives in hemoglobin adducts analysis: selective digestion with Calpain I

Pieri¹

2014

PER

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Background: hemoglobin adducts are considered suitable biomarkers to evaluate human exposure to electrophile agents. One of the procedures used for the molecular dosimetry of hemoglobin adducts is the enzymatic digestion of the protein and the subsequent quantification of modified peptides by mass spectrometry. The aim of the study is to evaluate the ability of Calpain to discriminate between normal and alkylated globin chains. Methods: digestions of pure hemoglobin sample and of an alkylated one with Calpain I at 200:1 and 25:1 weight ratios, for 1, 5 and 18 hrs were carried out. Only the standard deviations (SD) of the ratios between alkylated globins with respect to the unmodified ones (αECH/α and bECH/b) were estimated because the aim of the study is to assess the ability of Calpain I to selectively digest the samples and, above all, to find the optimal digestion conditions and characterize obtained peptides. Results: by using a 200:1 weight ratio only peptides α(1-137), α(1-138) and b(1-142) were produced, pointing out that the first proteolytic sites are located at the C-terminus ends of both α-and b-chains. The identification of peptides obtained from the 25:1 digestions allowed the determination of internal secondary proteolytic sites, not reported in literature. In both cases, a non-negligible proteolysis was observed only when a reaction time of 18 hrs was used. Discussion: results showed a progressive enrichment of modified hemoglobin with respect to the unmodified one, particularly for the α-chain and represent a promising initial step in the development of a selective purification procedure to be applied to protein adducts analysis.

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Analysis of Hemoglobin Adducts from Acrylamide, Glycidamide, and Ethylene Oxide in Paired Mother/Cord Blood Samples from Denmark

Cited by 82 publications

References 56 publications

Scientific Opinion on acrylamide in food

Scientific Opinion on acrylamide in food

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

New perspectives in hemoglobin adducts analysis: selective digestion with Calpain I

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