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  • 51. O'Callaghan-Gordo, Cristina
    et al.
    Kogevinas, Manolis
    Pedersen, Marie
    Fthenou, Eleni
    Espinosa, Ana
    Tsiapa, Xristina
    Chalkiadaki, Georgia
    Daraki, Vasiliki
    Dermitzaki, Eirini
    Decordier, Ilse
    Farmer, Peter B.
    Georgiadis, Panagiotis
    Georgiou, Vaggelis
    Kyrtopoulos, Soterios A.
    Merlo, Domenico Franco
    Romaguera, Dora
    Roumeliotaki, Theano
    Sarri, Katerina
    Törnqvist, Margareta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljövetenskap och analytisk kemi.
    Vande Loock, Kim
    von Stedingk, Hans
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljövetenskap och analytisk kemi.
    Kleinjans, Jos
    Kirsch-Volders, Micheline
    Chatzi, Leda
    Maternal diet during pregnancy and micronuclei frequency in peripheral blood T lymphocytes in mothers and newborns (Rhea cohort, Crete)2018Ingår i: European Journal of Nutrition, ISSN 1436-6207, E-ISSN 1436-6215, Vol. 57, nr 1, s. 209-218Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose The study assessed whether diet and adherence to cancer prevention guidelines during pregnancy were associated with micronucleus (MN) frequency in mothers and newborns. MN is biomarkers of early genetic effects that have been associated with cancer risk in adults. Methods A total of 188 mothers and 200 newborns from the Rhea cohort (Greece) were included in the study. At early-mid pregnancy, we conducted personal interviews and a validated food frequency questionnaire was completed. With this information, we constructed a score reflecting adherence to the World Cancer Research Fund/American Institute for Cancer Research cancer prevention guidelines on diet, physical activity and body fatness. At delivery, maternal and/or cord blood was collected to measure DNA and hemoglobin adducts of dietary origin and frequencies of MN in binucleated and mononucleated T lymphocytes (MNBN and MNMONO). Results In mothers, higher levels of red meat consumption were associated with increased MNBN frequency [2nd tertile IRR = 1.34 (1.00, 1.80), 3rd tertile IRR = 1.33 (0.96, 1.85)] and MNMONO frequency [2nd tertile IRR = 1.53 (0.84, 2.77), 3rd tertile IRR = 2.69 (1.44, 5.05)]. The opposite trend was observed for MNBN in newborns [2nd tertile IRR = 0.64 (0.44, 0.94), 3rd tertile IRR = 0.68 (0.46, 1.01)], and no association was observed with MNMONO. Increased MN frequency in pregnant women with high red meat consumption is consistent with previous knowledge. Conclusions Our results also suggest exposure to genotoxics during pregnancy might affect differently mothers and newborns. The predictive value of MN as biomarker for childhood cancer, rather than adulthood, remains unclear. With few exceptions, the association between maternal carcinogenic exposures during pregnancy and childhood cancer or early biologic effect biomarkers remains poorly understood.

  • 52. Pedersen, Marie
    et al.
    Schoket, Bernadette
    Godschalk, Roger W.
    Wright, John
    von Stedingk, Hans
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK), Avdelningen för miljökemi.
    Törnqvist, Margareta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK), Avdelningen för miljökemi.
    Sunyer, Jordi
    Nielsen, Jeanette K.
    Merlo, Domenico F.
    Mendez, Michelle A.
    Meltzer, Helle M.
    Lukacs, Viktoria
    Landström, Anette
    Kyrtopoulos, Soterios A.
    Kovacs, Katalin
    Knudsen, Lisbeth E.
    Haugen, Margaretha
    Hardie, Laura J.
    Gutzkow, Kristine B.
    Fleming, Sarah
    Fthenou, Eleni
    Farmer, Peter B.
    Espinosa, Aina
    Chatzi, Leda
    Brunborg, Gunnar
    Brady, Nigel J.
    Botsivali, Maria
    Arab, Khelifa
    Anna, Livia
    Alexander, Jan
    Agramunt, Silvia
    Kleinjans, Jos C.
    Segerbäck, Dan
    Kogevinas, Manolis
    Bulky DNA Adducts in Cord Blood, Maternal Fruit-and-Vegetable Consumption, and Birth Weight in a European Mother-Child Study (NewGeneris)2013Ingår i: Journal of Environmental Health Perspectives, ISSN 0091-6765, E-ISSN 1552-9924, Vol. 121, nr 10, s. 1200-1206Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Tobacco-smoke, airborne, and dietary exposures to polycyclic aromatic-hydrocarbons (PAHs) have been associated with reduced prenatal growth. Evidence from -biomarker-based studies of low-exposed populations is limited. Bulky DNA adducts in cord blood reflect the prenatal effective dose to several genotoxic agents including PAHs. Objectives: We estimated the association between bulky DNA adduct levels and birth weight in a multicenter study and examined modification of this association by maternal intake of fruits and vegetables during pregnancy. Methods: Pregnant women from Denmark, England, Greece, Norway, and Spain were recruited in 2006-2010. Adduct levels were measured by the 32P-postlabeling technique in white blood cells from 229 mothers and 612 newborns. Maternal diet was examined through questionnaires. Results: Adduct levels in maternal and cord blood samples were similar and positively correlated (median, 12.1 vs. 11.4 adducts in 108 nucleotides; Spearman rank correlation coefficient = 0.66, p < 0.001). Cord blood adduct levels were negatively associated with birth weight, with an estimated difference in mean birth weight of -129 g (95% CI: -233, -25 g) for infants in the highest versus lowest tertile of adducts. The negative association with birth weight was limited to births in Norway, Denmark, and England, the countries with the lowest adduct levels, and was more pronounced in births to mothers with low intake of fruits and vegetables (-248 g; 95% CI: -405, -92 g) compared with those with high intake (-58 g; 95% CI: -206, 90 g). Conclusions: Maternal exposure to genotoxic agents that induce the formation of bulky DNA adducts may affect intrauterine growth. Maternal fruit and vegetable consumption may be protective.

  • 53. Pedersen, Marie
    et al.
    von Stedingk, Hans
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Botsivali, Maria
    Agramunt, Silvia
    Alexander, Jan
    Brunborg, Gunnar
    Chatzi, Leda
    Fleming, Sarah
    Fthenou, Eleni
    Granum, Berit
    Gutzkow, Kristine B.
    Hardie, Laura J.
    Knudsen, Lisbeth E.
    Kyrtopoulos, Soterios A.
    Mendez, Michelle A.
    Merlo, Domenico F.
    Nielsen, Jeanette K.
    Rydberg, Per
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Segerback, Dan
    Sunyer, Jordi
    Wright, John
    Törnqvist, Margareta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Kleinjans, Jos C.
    Kogevinas, Manolis
    Birth Weight, Head Circumference, and Prenatal Exposure to Acrylamide from Maternal Diet: The European Prospective Mother-Child Study (NewGeneris)2012Ingår i: Journal of Environmental Health Perspectives, ISSN 0091-6765, E-ISSN 1552-9924, Vol. 120, nr 12, s. 1739-1745Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 54. Pellè, Lucia
    et al.
    Carlsson, Henrik
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljövetenskap och analytisk kemi.
    Cipollini, Monica
    Bonotti, Alessandra
    Foddis, Rudy
    Cristaudo, Alfonso
    Romei, Cristina
    Elisei, Rossella
    Gemignani, Federica
    Törnqvist, Margareta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljövetenskap och analytisk kemi.
    Landi, Stefano
    The polymorphism rs2480258 within CYP2E1 is associated with different rates of acrylamide metabolism in vivo in humans2018Ingår i: Archives of Toxicology, ISSN 0340-5761, E-ISSN 1432-0738, Vol. 92, nr 6, s. 2137-2140Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In a recent study, we demonstrated that the variant allele of rs2480258 within intron VIII of CYP2E1 is associated with reduced levels of mRNA, protein, and enzyme activity. CYP2E1 is the most important enzyme in the metabolism of acrylamide (AA) by operating its oxidation into glycidamide (GA). AA occurs in food, is neurotoxic and classified as a probable human carcinogen. The goal of the present study was to further assess the role of rs2480258 by measuring the rate of AA > GA biotransformation in vivo. In blood samples from a cohort of 120 volunteers, the internal doses of AA and GA were assessed by AA and GA adducts to hemoglobin (Hb) measured by mass spectrometry. The rate of biotransformation was assessed by calculating the GA-Hb/AA-Hb ratio. To maximize the statistical power, 60 TT was compared to 60 CC-homozygotes and the results showed that TT homozygotes had a statistically significant reduced rate of biotransformation. Present results reinforced the notion that T-allele of rs2480258 is a marker of low functional activity of CYP2E1. Moreover, we studied the role of polymorphisms (SNPs) within glutathione-S-transferases (GSTs) enzymes and epoxide hydrolase (EPHX), verifying previous findings that SNPs within GSTs and EPHX influence the metabolism rate.

  • 55.
    Törnqvist, Margareta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Estimated acrylamide intakes and haemoglobin acrylamide adducts: Experience from human studies: ECNIS, WP1 Workshop Report 62008Ingår i: WP1 workshop on progressing from transitional to large-scale molecular epidemiology studies:: Cavtat, Croatia, 21 September, 2008, 2008Konferensbidrag (Övrig (populärvetenskap, debatt, mm))
  • 56.
    Törnqvist, Margareta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Forskning kring kemiska ämnens toxiska effekter har blivit nedprioriterad2008Övrigt (Övrig (populärvetenskap, debatt, mm))
  • 57.
    Törnqvist, Margareta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Wer hat noch Angst vor Acrylamid2007Övrigt (Övrig (populärvetenskap, debatt, mm))
  • 58.
    Törnqvist, Margareta
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Paulsson, Birgit
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Vickström, Anna
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Granath, Fredrik
    Dietary acrylamide and cancer risk estimation on the basis of toxicological data2007Ingår i: Division of Agricultural and Food Chemistry: the CORNUCOPIA, 2007Konferensbidrag (Övrigt vetenskapligt)
  • 59.
    Törnqvist, Margareta
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Paulsson, Birgit
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Vikström, Anna C.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Granath, Fredrik
    Approach for cancer risk estimation of acrylamide in food on the basis of animal cancer tests and in vivo dosimetry2008Ingår i: Journal of Agricultural and Food Chemistry, ISSN 0021-8561, E-ISSN 1520-5118, Vol. 56, nr 15, s. 6004-6012Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The question about the contribution from acrylamide (AA) in food to the cancer risk in the general population has not yet had a satisfactory answer. One point of discussion is whether AA constitutes a cancer risk through its genotoxic metabolite, glycidamide (GA), or whether other mechanism(s) could be operating. Using a relative cancer risk model, an improvement of the cancer risk estimate for dietary AA can be obtained by estimation of the genotoxic contribution to the risk. One cornerstone in this model is the in vivo dose of the causative genotoxic agent. This paper presents an evaluation, according to this model, of published AA cancer tests on the basis of in vivo doses of GA in rats exposed in the cancer tests. The present status regarding data with importance for an improved estimation of the contribution from GA to the cancer risk of AA, such as in vivo doses measured in humans, is discussed.

  • 60.
    Vikström, A.C.
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK), Avdelningen för miljökemi.
    Abramsson-Zetterberg, L.
    Athanassiadis, I.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Granath, F.
    Törnqvist, M.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    In vivo doses of acrylamide and glycidamide in humans after intake of acrylalmide-rich food2011Ingår i: Toxicological Sciences, ISSN 1096-6080, E-ISSN 1096-0929, Vol. 119, nr 1, s. 41-49Artikel i tidskrift (Refereegranskat)
  • 61.
    Vikström, A.C.
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Paulsson, B.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Axmon, A.
    Warholm, M.
    Wirfält, E.
    Törnqvist, M.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    In vivo doses from acrylamide in food – variation between and within individualsManuskript (preprint) (Övrigt vetenskapligt)
  • 62.
    Vikström, Anna C.
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Abramsson-Zetterberg, Lilianne
    Naruszewicz, Marek
    Athanassiadis, Ioannis
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Granath, Fredrik N.
    Törnqvist, Margareta A.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    In Vivo Doses of Acrylamide and Glycidamide in Humans after Intake of Acrylamide-Rich Food2011Ingår i: Toxicological Sciences, ISSN 1096-6080, E-ISSN 1096-0929, Vol. 119, nr 1, s. 41-49Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    For assessment of cancer risk from acrylamide (AA) exposure through food, the relation between intake from food in humans and the in vivo doses (area under the concentration-time curve, AUC) of AA (AUC-AA) and of its genotoxic metabolite glycidamide (GA) (AUC-GA) is used as a basis for extrapolation between exposure levels and between species. In this study, AA-rich foods were given to nonsmokers: a high intake of 11 mu g AA/kg body weight (bw) and day for 4 days or an extra (medium) intake of 2.5 mu g AA/kg bw and day for a month. Hemoglobin (Hb)-adduct levels from AA and GA, measured in blood samples donated before and after exposures, were used for calculation of AUC-AA and AUC-GA using reaction rate constants for the adduct formation measured in vitro. Both AA- and GA-adduct levels increased about twofold after the periods with enhanced intake. AUC for the high and medium groups, respectively, in nanomolar hours per microgram AA per kilogram bw, was for AA 212 and 120 and for GA 49 and 21. The AA intake in the high group was better controlled and used for comparisons with other data. The AUCs per exposure dose obtained in the present human study (high group) are in agreement with those previously obtained at 10(2) times higher exposure levels in humans. Furthermore, the values of AUC-AA and AUC-GA are five and two times higher, respectively, than the corresponding values for F344 rats exposed to AA at levels as in published cancer bioassays.

  • 63.
    Vikström, Anna C.
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Eriksson, Sune
    Paulsson, Birgit
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Karlsson, Patrik
    Athanassiadis, Ioannis
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Törnqvist, Margareta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Internal doses of acrylamide and glycidamide in mice fed diets with low acrylamide contents2008Ingår i: Molecular Nutrition & Food Research, ISSN 1613-4125, E-ISSN 1613-4133, Vol. 52, nr 8, s. 974-980Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The formation of acrylamide during heating of certain foodstuffs constitutes a potential health hazard. The health risk assessment should be based on knowledge about the relation between dietary exposure to acrylamide and internal doses of acrylamide and its genotoxic metabolite glycidamide. The primary aim of this study in mice was to measure these relationships at low levels of acrylamide intake through the diet. A secondary aim was to clarify which extraction method should be used when analyzing acrylamide in food in order to obtain a correct measure of the acrylamide that is available for absorption. In the analysis procedure, alkaline extraction has earlier shown much higher measured acrylamide levels in certain foods compared to water extraction. In this subcronic study the administered diets were composed to give five levels of acrylamide intakes between 3 and 50 mug/kg body weight per day (calculated on figures obtained after water extraction). Internal doses of acrylamide and glycidamide were measured through hemoglobin (Hb)-adducts. The results showed linear relationships between the exposure of acrylamide and Hb-adduct levels from both acrylamide and glycidamide at these low exposure levels. The study also showed that the &quot;extra&quot; acrylamide measured with alkaline extraction does not correspond to bioavailable acrylamide.

  • 64.
    Vikström, Anna C.
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK), Avdelningen för miljökemi.
    Warholm, Margareta
    Paulsson, Birgit
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK), Avdelningen för miljökemi.
    Axmon, Anna
    Wirfalt, Elisabet
    Törnqvist, Margareta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK), Avdelningen för miljökemi.
    Hemoglobin adducts as a measure of variations in exposure to acrylamide in food and comparison to questionnaire data2012Ingår i: Food and Chemical Toxicology, ISSN 0278-6915, E-ISSN 1873-6351, Vol. 50, nr 7, s. 2531-2539Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Measurement of haemoglobin (Hb) adducts from acrylamide (AA) and its metabolite glycidamide (GA) is a possibility to improve the exposure assessment in epidemiological studies of AA intake from food. This study aims to clarify the reliability of Hb-adduct measurement from individual single samples for exposure assessment of dietary AA intake. The intra-individual variations of AA- and GA-adduct levels measured in blood samples collected over 20 months from 13 non-smokers were up to 2-fold and 4-fold, respectively. The corresponding interindividual variations observed between 68 non-smokers, with large differences in AA intake, were 6-fold and 8-fold, respectively. The intra-individual variation of the GA-to-AA-adduct level ratio was up to 3-fold, compared to 11-fold between individuals (n = 68). From AA-adduct levels the average AA daily intake (n = 68) was calculated and compared to that estimated from dietary history methodology: 0.52 and 0.67 mu g/kg body weight and day, respectively. At an individual level the measures showed low association (Rs = 0.39). Conclusions: Dietary AA is the dominating source to measured AA-adduct levels and corresponding inter- and intra-individual variations in non-smokers. Measurements from single individual samples are useful for calculation of average M intake and its variation in a cohort, and for identification of individuals only from extreme intake groups.

  • 65.
    Vikström, Anna C.
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK), Avdelningen för miljökemi.
    Wilson, Kathryn M.
    Paulsson, Birgit
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK), Avdelningen för miljökemi.
    Athanassiadis, Ioannis
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK), Avdelningen för miljökemi.
    Grönberg, Henrik
    Adami, Hans-Olov
    Adolfsson, Jan
    Mucci, Lorelei A.
    Bälter, Katarina
    Törnqvist, Margareta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK), Avdelningen för miljökemi.
    Alcohol influence on acrylamide to glycidamide metabolism assessed with hemoglobin-adducts and questionnaire data2010Ingår i: Food and Chemical Toxicology, ISSN 0278-6915, E-ISSN 1873-6351, Vol. 58, nr 3, s. 820-824Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Our purpose was to investigate whether alcohol (ethanol) consumption could have an influence on the metabolism of acrylamide to glycidamide in humans exposed to acrylamide through food. We studied a subsample from a population-based case–control study of prostate cancer in Sweden (CAPS). Questionnaire data for alcohol intake estimates was compared to the ratio of hemoglobin-adduct levels for acrylamide and glycidamide, used as a measure of individual differences in metabolism. Data from 161 non-smoking men were processed with regard to the influence of alcohol on the metabolism of acrylamide to glycidamide. A negative, linear trend of glycidamide-adduct to acrylamide-adduct-level ratios with increasing alcohol intake was observed and the strongest association (p-value for trend = 0.02) was obtained in the group of men with the lowest adduct levels (⩽47 pmol/g globin) when alcohol intake was stratified by acrylamide-adduct levels. The observed trend is likely due to a competitive effect between ethanol and acrylamide as both are substrates for cytochrome P450 2E1. Our results, strongly indicating that ethanol influence metabolism of acrylamide to glycidamide, partly explain earlier observations of only low to moderate associations between questionnaire data on dietary acrylamide intake and hemoglobin-adduct levels.

  • 66.
    von Stedingk, Hans
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Davies, Ronnie
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Rydberg, Per
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Törnqvist, Margareta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Methyl vinyl ketone – identification and quantification of adduct to N-terminal valine in human haemoglobin2010Ingår i: Journal of chromatography. B, ISSN 1570-0232, E-ISSN 1873-376X, Vol. 878, nr 27, s. 2491-2496Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Adducts to N-terminal valines in Hb have been shown useful as biomarkers of exposure to electrophilic compounds. Adducts from many compounds have earlier been measured with a modified Edman degradation method using a GC–MS/MS method. A recently developed method, the adduct FIRE procedure™, adopted for analysis by LC–MS/MS, has been applied in this study. With this method a fluorescein isothiocyanate (FITC) reagent is used to measure adducts (R) from electrophiles with a modified Edman procedure. By using LC–MS/MS in product ion scan mode, a new peak was identified and the obtained MS data indicated that this adduct could originate from methyl vinyl ketone (MVK). Incubation of human-, sheep- and bovine blood with MVK increased the signal of the identified peak. By comparing the LC–MS/MS data from the unknown background peak with data obtained from synthesized fluorescein thiohydantoin (FTH) standards of the MVK adduct to valine and d8-valine, the identity of this adduct was confirmed. The MVK adduct was shown present in human blood (35 pmol/g globin, n = 3) and only just above LOD in bovine blood, n = 1 (LOD = 2 pmol/g globin). MVK reacts, in similarity with acrylamide, via Michael addition. MVK is known to occur in the environment and has earlier been observed in biological samples, which means that there are possible natural and anthropogenic exposure sources. Analysis of an Hb adduct from MVK in humans has to our knowledge not been described before.

  • 67.
    von Stedingk, Hans
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Osterman-Golkar, Siv
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Törnqvist, Margareta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Hemoglobin adducts2011Ingår i: Biomarkers and Human Biomonitoring. Vol. 2 : Selected biomarkers of current interest / [ed] Lisbet E. Knudsen and Domenico Franco Merlo, Cambridge: Royal Society of Chemistry , 2011, s. 1-22Kapitel i bok, del av antologi (Övrigt vetenskapligt)
  • 68.
    von Stedingk, Hans
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Rydberg, Per
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Mose, Tina
    Pedersen, Marie
    Knudsen, Lisbeth
    Törnqvist, Margareta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Biomarkers of exposure- analysis of Haemoglobin adducts formed from acrylamide, glycidamide and ethylene oxide in pregnent mothers and cord blood2008Ingår i: European Environmental Mutagen Society: 38th annual meeting, 2008, s. 284-Konferensbidrag (Övrigt vetenskapligt)
  • 69.
    von Stedingk, Hans
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Rydberg, Per
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Törnqvist, Margareta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    A new modified Edman procedure for analysis of N-terminal valine adducts in hemoglobin by LC-MS/MS2010Ingår i: Journal of chromatography. B, ISSN 1570-0232, E-ISSN 1873-376X, Vol. 878, nr 27, s. 2483-2490Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A rapid and sensitive method using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for simultaneous determination of adducts from acrylamide, glycidamide and ethylene oxide to N-terminal valines in hemoglobin (Hb) was developed. This new procedure is based on the same principles as the N-alkyl Edman procedure for analysis of adducts from electrophilic agents to N-terminal valines in Hb. The N-substituted valines can be detached, enriched and measured selectively as thiohydantoins by the use of an Edman reagent, in this case fluorescein isothiocyanate (FITC). This procedure is denoted as the "adduct FIRE procedure" as the FITC reagent is used for measurement of adducts ((R) under bar) formed from electrophilic compounds with a modified Edman procedure. In this study, fluorescein thiohydantoin (FTH) analytes of N-substituted valines from acrylamicle, glycidamide and ethylene oxide, as well as their corresponding hepta- and tri-deuterium-substituted analogues, were synthesized. These analytes (n = 8) were then characterized by LC-MS/MS (ESI, positive ion mode) and obtained product ions were interpreted. A considerable work with optimization of the FIRE procedure (TM), resulted in a procedure in which low background levels of the studied adducts could be measured from 250 mu L lyzed whole blood samples (human non-smokers). The analytes were enriched and purified with solid phase extraction columns and analyzed by LC-MS/MS with LOQ clown to 1 pmol adduct/g Hb. Compared to other procedures for determination of N-terminal Hb adducts, the introduction of FITC has led to a simplified procedure, where whole blood also can be used, giving new opportunities and reduced hand on time with increased sample throughput.

  • 70.
    von Stedingk, Hans
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK), Avdelningen för miljökemi.
    Vikström, Anna
    Rydberg, Per
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Pedersen, Marie
    Nielsen, Jeanette K.S.
    Segerbäck, Dan
    Törnqvist, Margareta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Analysis of hemoglobin adducts from acrylamide, glycidamide and ethylene oxide in paired mother/cordblood samples from Denmark2011Ingår i: Chemical Research in Toxicology, ISSN 0893-228X, E-ISSN 1520-5010, Vol. 24, nr 11, s. 1957-1965Artikel i tidskrift (Refereegranskat)
    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.

  • 71.
    Westberg, Emelie
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Hedebrant, Ulla
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Fred, Charlotta
    Törnqvist, Margareta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Karaktärisering av PAH-addukter till histidin och lysin i humant serum albumin (HSA) med LC-MS/MS2007Ingår i: Svensk-norsk miljökjemisk vintermöte: Dr. Holms Hotell, Geilo, Norge, 2007, s. 40-Konferensbidrag (Övrigt vetenskapligt)
  • 72.
    Westberg, Emelie
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Hedebrant, Ulla
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Haglund, Johanna
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Alsberg, Tomas
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för tillämpad miljövetenskap (ITM).
    Eriksson, Johan
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Seidel, Albrecht
    Törnqvist, Margareta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Conditions for sample preparation and quantitative HPLC/MS-MS analysis of bulky adducts to serum albumin with diolepoxides of polycyclic aromatic hydrocarbons as models2014Ingår i: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 406, nr 5, s. 1519-1530Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Stable adducts to serum albumin (SA) from electrophilic and genotoxic compounds/metabolites can be used as biomarkers for quantification of the corresponding in vivo dose. In the present study, conditions for specific analysis of stable adducts to SA formed from carcinogenic polycyclic aromatic hydrocarbons (PAH) were evaluated in order to achieve a sensitive and reproducible quantitative method. Bulky adducts from diolepoxides (DE) of PAH, primarily DE of benzo[a]pyrene (BPDE) and also DE of dibenzo[a,l]pyrene (DBPDE) and dibenzo[a,h]anthracene (DBADE), were used as model compounds. The alkylated peptides obtained after enzymatic hydrolysis of human SA modified with the different PAHDE were principally PAHDE-His-Pro, PAHDE-His-Pro-Tyr and PAHDE-Lys. Alkaline hydrolysis under optimised conditions gave the BPDE-His as the single analyte of alkylated His, but also indicated degradation of this adduct. It was not possible to obtain the BPDE-His as one analyte from BPDE-alkylated SA through modifications of the enzymatic hydrolysis. The BPDE-His adduct was shown to be stable during the weak acidic conditions used in the isolation of SA. Enrichment by HPLC or SPE, but not butanol extraction, gave good recovery, using Protein LoBind tubes. A simple internal standard (IS) approach using SA modified with other PAHDE as IS was shown to be applicable. A robust analytical procedure based on digestion with pronase, enrichment by HPLC or SPE, and analysis with HPLC/MS-MS electrospray ionisation was achieved. A good reproducibility (coefficient of variation (CV) 11 %) was obtained, and the achieved limit of detection for the studied PAHDE, using standard instrumentation, was approximately 1 fmol adduct/mg SA analysing extract from 5 mg SA.

  • 73.
    Westberg, Emelie
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK), Avdelningen för miljökemi.
    Motwani, Hitesh
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK), Avdelningen för miljökemi.
    Lindh, Christian
    Abramsson-Zetterberg, Lilianne
    Törnqvist, Margareta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK), Avdelningen för miljökemi.
    Comparison of specific biomarkers of internal dose and genotoxic effect after exposure to BP with the aim to use in risk assessmentManuskript (preprint) (Övrigt vetenskapligt)
  • 74. Wilson, Kathryn M.
    et al.
    Bälter, Katarina
    Adami, Hans-Olov
    Grönberg, Henrik
    Vikström, Anna C.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Paulsson, Birgit
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Törnqvist, Margareta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Mucci, Lorelei A.
    Acrylamide exposure measured by food frequency questionnaire and hemoglobin adduct levels and prostate cancer risk in the Cancer of the Prostate in Sweden Study2009Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 124, nr 10, s. 2384-2390Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Acrylamide, a probable human carcinogen, is formed during the cooking of many commonly consumed foods. Data are scant on whether dietary acrylamide represents an important cancer risk in humans. We studied the association between acrylamide and prostate cancer risk using 2 measures of acrylamide exposure: intake from a food frequency questionnaire (FFQ) and acrylamide adducts to hemoglobin. We also studied the correlation between these 2 exposure measures. We used data from the population-based case-control study Cancer of the Prostate in Sweden (CAPS). Dietary data was available for 1,499 cases and 1,118 controls. Hemoglobin adducts of acrylamide were measured in blood samples from a subset of 170 cases and 161 controls. We calculated odds ratios (ORs) for the risk of prostate cancer in high versus low quantiles of acrylamide exposure using logistic regression. The correlation between FFQ acrylamide intake and acrylamide adducts in non-smokers was 0.25 (95% confidence interval: 0.14-0.35), adjusted for age, region, energy intake, and laboratory batch. Among controls the correlation was 0.35 (95% CI: 0.21-0.48); among cases it was 0.15 (95% CI: 0.00-0.30). The OR of prostate cancer for the highest versus lowest quartile of acrylamide adducts was 0.93 (95% CI: 0.47-1.85, p-value for trend = 0.98). For FFQ acrylamide, the OR of prostate cancer for the highest versus lowest quintile was 0.97 (95% CI: 0.75-1.27, p trend = 0.67). No significant associations were found between acrylamide exposure and risk of prostate cancer by stage, grade, or PSA level. Acrylamide adducts to hemoglobin and FFQ-measured acrylamide intake were moderately correlated. Neither measure of acrylamide exposure-hemoglobin adducts or FFQ-was associated with risk of prostate cancer.

  • 75. Wilson, Kathryn M.
    et al.
    Vesper, Hubert W.
    Tocco, Paula
    Sampson, Laura
    Rosén, Johan
    Hellenäs, Karl-Erik
    Törnqvist, Margareta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Willett, Walter C.
    Validation of a food frequency questionnaire measurement of dietary acrylamide intake using hemoglobin adducts of acrylamide and glycidamide2009Ingår i: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 20, nr 3, s. 269-278Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Acrylamide, a probable human carcinogen, is formed during high-heat cooking of many common foods. The validity of food frequency questionnaire (FFQ) measures of acrylamide intake has not been established. We assessed the validity of acrylamide intake calculated from an FFQ using a biomarker of acrylamide exposure. METHODS: We calculated acrylamide intake from an FFQ in the Nurses' Health Study II. We measured hemoglobin adducts of acrylamide and its metabolite, glycidamide, in a random sample of 342 women. Correlation and regression analyses were used to assess the relationship between acrylamide intakes and adducts. RESULTS: The correlation between acrylamide intake and the sum of acrylamide and glycidamide adducts was 0.31 (95% CI: 0.20-0.41), adjusted for laboratory batch, energy intake, and age. Further adjustment for BMI, alcohol intake, and correction for random within-person measurement error in adducts gave a correlation of 0.34 (CI: 0.23-0.45). The intraclass correlation coefficient for the sum of adducts was 0.77 in blood samples collected 1-3 years apart in a subset of 45 women. Intake of several foods significantly predicted adducts in multiple regression. CONCLUSIONS: Acrylamide intake and hemoglobin adducts of acrylamide and glycidamide were moderately correlated. Within-person consistency in adducts was high over time.

  • 76. Wirfält, E
    et al.
    Paulsson, B
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Törnqvist, M
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Axmon, A
    Hagmar, L
    Associations between estimated acrylamide intakes, and hemoglobin AA adducts in a sample from the Malmö Diet and Cancer cohort2008Ingår i: European Journal of Clinical Nutrition, Vol. 62, s. 314-323Artikel i tidskrift (Refereegranskat)
  • 77.
    Zurita, Javier
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljövetenskap och analytisk kemi.
    Motwani, Hitesh V.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljövetenskap och analytisk kemi.
    Ilag, Leopold L.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljövetenskap och analytisk kemi.
    Souliotos, Vassilis L
    Kyrtopoulos, Soterios A
    Nilsson, Ulrika
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljövetenskap och analytisk kemi.
    Törnqvist, Margareta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljövetenskap och analytisk kemi.
    Detection of benzo[a]pyrene diol epoxide adducts to histidine and lysine in serum albumin in vivo by high-resolution-tandem mass spectrometryManuskript (preprint) (Övrigt vetenskapligt)
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