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Immunological Methods for Dosimetry of Heterocyclic Amines

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Toxicology - From Cells to Man

Part of the book series: Archives of Toxicology ((TOXICOLOGY,volume 18))

Abstract

Carcinogenic heterocyclic amines are formed by common household cooking procedures, and it is therefore of interest to evaluate exposures in the general population. High-affinity monoclonal antibodies to 2-amino-l-methyl-6-phenyl- imidazo[4,5-b]pyridine (PhIP1) were produced and a sensitive fluorescence-based ELISA assay developed with a 50% inhibition by 150 fmoles PhIP or PhlP- metabolites modified in the 2-position. PhIP antigenic material was excreted mainly from 0-24 hours after a single meal containing fried meat in two volunteers and dropped to background levels after 48 hours. Urine samples (24 hours) were collected from 265 Danish males and females aged 40-70 years. The participants were also asked to fill in a questionnaire regarding their recent intake of fried and otherwise cooked meat. Excretion of PhlP-antigenic material was observed among those who had been eating Med meat with a median excretion of 1.5μg/24 hours. A higher median excretion among all samples of about 2.3μg/24 hours was observed when acid hydrolyzed samples were analyzed. This indicates that a large proportion of conjugated metabolites are present before hydrolysis, since these metabolites are not as efficient competitors for the antibody in ELISA. The excretion of PhIP antigenic materials showed a skewed normal distribution. These observations are close to predicted exposure rates in the general population, based on food consumption figures and analyses of PhIP in fried meat samples. PhIP antigenic material was always found to be present in urine samples from individuals who reported a recent intake of fried meat. Positive samples were also found among individuals who reported no recent intakes of fried or browned meat. The possible sources of this exposure are discussed.

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Abbreviations

ELISA:

enzyme-linked immunosorbent assay

MAb:

monoclonal antibody

MelQ:

2-amino-3,4-dimethylimidazo[4,5-f]quinoline; 8-MeIQx, 2-amino-3,8- dimethylimidazo[4,5-f]quinoxaline

N2-OH-PhIP:

2-hydroxylamino-l -methyl-6-phenyl- imidazo[4,5-£]pyridine

4’-OH-PhIP:

2-amino-l-methyl-6-(4-hydroxyphenyl)imidazo[4,5- 6]pyridine

PBS:

phosphate buffered saline

PBS-T:

PBS with 0.05% Tween 20

PhIP:

2- amino-l-methyl-6-phenylimidazo[4,5-b]pyridine.

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Author information

Authors and Affiliations

  1. Institute of Toxicology, National Food Agency of Denmark, Denmark

    L. O. Dragsted, S. E. Nielsen & H. Frandsen

  2. Glostrup population studies, Medical Department C, Glostrup Hospital, University of Copenhagen, Denmark

    L. O. Dragsted, S. E. Nielsen & H. Frandsen

  3. Danish Epidemiology Science Center at the Institute of preventive Medicine, Copenhagen Hospital Corporation, Kommunehospitalet, Copenhagen, Denmark

    B. L. Heitmann

  4. Department of Chemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden

    S. Grivas

Authors
  1. L. O. Dragsted
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  2. S. E. Nielsen
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  3. B. L. Heitmann
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  4. S. Grivas
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  5. H. Frandsen
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Editor information

Editors and Affiliations

  1. Interkantonale Kontrollstelle für Heilmittel, Erlachstrasse 8, CH-3000, Bern 9, Switzerland

    Jürg P. Seiler

  2. Department of Pharmacology, Charles University of Prague, 3rd Medical School, Ruská 87, Czech Republic

    Olga Kroftová

  3. Department of Pharmacology, Charles University, Faculty of Medicine, Karlovarská 48, CZ-30166, Pilsen, Czech Republic

    Vladislav Eybl

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© 1996 Springer-Verlag Berlin Heidelberg

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Dragsted, L.O., Nielsen, S.E., Heitmann, B.L., Grivas, S., Frandsen, H. (1996). Immunological Methods for Dosimetry of Heterocyclic Amines. In: Seiler, J.P., Kroftová, O., Eybl, V. (eds) Toxicology - From Cells to Man. Archives of Toxicology, vol 18. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-61105-6_26

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  • DOI: https://doi.org/10.1007/978-3-642-61105-6_26

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