Immunoaffinity purification of dietary heterocyclic amine carcinogens
- Lawrence Livermore National Lab., CA (United States)
Cooking meats produces a family of heterocyclic aromatic amines that are carcinogens in rodents and genotoxic in many short-term assays. Concern that these compounds may be human carcinogens has prompted us to develop immunochemical methods for quantifying these compounds in the human diet and for identifying the parent compounds and metabolites in urine and feces. Previously reported monoclonal antibodies to 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 6-phenyl-2-amino-1-methylimidazo[4,5-f]pyridine (PhIP) were used to purify by immunoaffinity these known mutagens and cross-reacting structural analogs from well-done cooked beef and urine samples. Materials recovered from the immunoaffinity columns were subsequently separated by HPLC to purify the known mutagens from cross-reacting chemicals that co-purify by immunoaffinity. Immunoaffinity chromatography was found to be a rapid means of quantifying individual known mutagens, with a minimum of precolumn sample clean-up required. In addition, this procedure has yielded several new mutagens present in cooked meats that are apparently structural analogs of PhIP. Immunoaffinity techniques were also used to purify metabolites from the urine of rats and humans exposed to MeIQx or PhIP. For MeIQx-exposed rats, the combination antibodies immunoconcentrated 75% of the total urinary radioactivity. Analysis of PhIP metabolites recovered from antibody columns is facilitated by the intrinsic fluorescence of PhIP and its metabolites, providing sufficient sensitivity to monitor individuals for the levels of PhIP excreted following consumption of typical western diets. 6 refs., 3 figs.
- DOE Contract Number:
- W-7405-ENG-48
- OSTI ID:
- 5896055
- Report Number(s):
- CONF-9110511-; CODEN: EVHPAZ; CNN: RO1 CA40811-03; UO1 CA48446-02
- Journal Information:
- Environmental Health Perspectives; (United States), Vol. 99; Conference: Symposium on biomonitoring and susceptibility markers in human cancer: applications in molecular epidemiology and risk assessment, Kailua-Kona, HI (United States), 26 Oct - 1 Nov 1991; ISSN 0091-6765
- Country of Publication:
- United States
- Language:
- English
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HETEROCYCLIC COMPOUNDS
BIOASSAY
CARCINOGENESIS
METABOLITES
BIOLOGICAL INDICATORS
CARCINOGENS
DIET
FECES
MONOCLONAL ANTIBODIES
MUTAGENS
RODENTS
URINE
ANIMALS
ANTIBODIES
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BODY FLUIDS
MAMMALS
MATERIALS
ORGANIC COMPOUNDS
PATHOGENESIS
VERTEBRATES
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550500* - Metabolism
550200 - Biochemistry