Development of aflatoxin B(1)-lysine adduct monoclonal antibody for human exposure studies

Appl Environ Microbiol. 2001 Jun;67(6):2712-7. doi: 10.1128/AEM.67.6.2712-2717.2001.

Abstract

Mouse monoclonal antibodies were developed against a synthetic aflatoxin B(1) (AFB)-lysine-cationized bovine serum albumin conjugate. The isotype of one of these antibodies, IIA4B3, has been classified as immunoglobulin G1(lambda). The affinity and specificity of IIA4B3 were further characterized by a competitive radioimmunoassay. The affinities of IIA4B3 for AFB and its associated adducts and metabolites are ranked as follows: AFB-lysine > 8,9-dihydro-8-(2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl formamido)-9-hydroxy-AFB > AFB = 8,9-dihydro-8-(N(7)-guanyl)-9-hydroxy-AFB > aflatoxin M(1) > aflatoxin Q(1). IIA4B3 had about a 10-fold higher affinity for binding to AFB-lysine adduct than to AFB when (3)H-AFB-lysine was used as the tracer. The concentration for 50% inhibition for AFB-lysine was 0.610 pmol; that for AFB was 6.85 pmol. IIA4B3 had affinities at least sevenfold and twofold higher than those of 2B11, a previously developed antibody against parent AFB, for the major aflatoxin-DNA adducts 8,9-dihydro-8-(N(7)-guanyl)-9-hydroxy-AFB and 8,9-dihydro-8-(2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl formamido)-9-hydroxy-AFB, respectively. An analytical method based on a competitive radioimmunoassay with IIA4B3 and (3)H-AFB-lysine was validated with a limit of detection of 10 fmol of AFB-lysine adduct. The method has been applied to the measurement of AFB-albumin adduct levels in human serum samples collected from the residents of areas at high risk for liver cancer.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aflatoxin B1 / analogs & derivatives*
  • Aflatoxin B1 / blood*
  • Aflatoxin B1 / immunology*
  • Antibodies, Monoclonal
  • Antigens
  • Binding, Competitive
  • Carcinogens, Environmental / analysis*
  • Environmental Exposure
  • Humans
  • Lysine / immunology
  • Radioimmunoassay / methods*
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Serum Albumin, Bovine / immunology

Substances

  • Antibodies, Monoclonal
  • Antigens
  • Carcinogens, Environmental
  • Serum Albumin, Bovine
  • Aflatoxin B1
  • Lysine