title: Monoclonal antibody development for acrylamide-adducted human haemoglobin; a biomarker of dietary acrylamide exposure.
abstract: The spontaneous formation of the neurotoxic carcinogen acrylamide in a wide range of cooked foods has recently been discovered, leading to dietary exposure estimates of 30.8 microg of acrylamide day(-1) for an average 77 kg human male. This is considerably higher than the European legal limit of acrylamide in drinking water, which is approximately 0.2 microg of acrylamide person(-1) day(-1). A recent study of 62,573 women over 11.3 years has observed an increased risk of postmenopausal endometrial and ovarian cancer (but not breast cancer) with increasing dietary acrylamide intake, demonstrating significant risk to human health. As individual acrylamide exposure is affected by dietary habits, cooking methods, and cigarette consumption; accurate extrapolation from estimated dietary exposure is extremely difficult. Quantifying biomarkers of acrylamide exposure therefore remains the most effective means of rapidly determining individual exposure to acrylamide, and correlating exposure with lifestyle choices. Current methodologies for the analysis of blood biomarkers of acrylamide are focused on expensive, slower chromatographic techniques such as GC and LC coupled to mass spectrometry. This paper describes the first successful development of two monoclonal antibodies specific to acrylamide-adducted haemoglobin (IC(50) of 94 ng ml(-1) and 198 ng ml(-1)), that are suitable for use in a high-throughput biomarker immunoassay to determine individual acrylamide exposure. Further development of acrylamide-haemoglobin standards with defined levels of acrylamide adduction will enable a fully quantitative assay, and allow sensitivity comparisons with alternative chromatographic methods of analysis.
authors.affiliation: Department of Biomedical Sciences, University of Liverpool, Sherrington Buildings, Ashton Street, Liverpool L69 3GE, UK. andrew_jpreston@hotmail.com
authors.forename: Andrew
authors.initials: A
authors.lastname: Preston
authors.forename: Terry
authors.initials: T
authors.lastname: Fodey
authors.forename: Alistair
authors.initials: A
authors.lastname: Douglas
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Elliott
mesh_terms: D020106:Acrylamide / Q000737:chemistry* / Q000276:immunology / Q000633:toxicity*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology; D015415:Biomarkers; D016889:Endometrial Neoplasms / Q000139:chemically induced / Q000276:immunology; D005260:Female; D005511:Food Handling; D006454:Hemoglobins / Q000032:analysis* / Q000737:chemistry / Q000276:immunology; D006801:Humans; D007118:Immunoassay / Q000379:methods / Q000592:standards; D051379:Mice; D008807:Mice, Inbred BALB C; D010051:Ovarian Neoplasms / Q000139:chemically induced / Q000276:immunology; D017698:Postmenopause / Q000276:immunology; D012015:Reference Standards
chemical_list: D000911:Antibodies, Monoclonal; D015415:Biomarkers; D006454:Hemoglobins; D020106:Acrylamide