Development and Evaluation of Exposure Biomarkers PAHs, PHIP and Aromatic Amines

$0P01FY2002ESNIH

Johns Hopkins University, Baltimore MD

Investigators

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Abstract

DESCRIPTION (provided by applicant): The long-term objective of this Project is to develop molecular biomarker strategies that are based on DNA and protein adducts and reveal exposure to carcinogens and their biologically effective dose in people. The hypothesis driving the research in this Project is that levels of specific biomarkers define exposure and biologically effective dose in susceptible individuals. The strategies will employ laser-induced fluorescence (LIF) for high performance liquid chromatography (HPLC) detection, with and without derivatization labeling, and mass spectrometric technologies, including electrospray HPLC-tandem mass spectroscopy (HPLC-MS-MS). Accelerator mass spectrometry (AMS) will be an important new technology introduced into the Program Project to facilitate the early-stage tracer experiments necessary for adduct identification and structure elucidation. This Project is designed to develop the advanced exposure assessment methods needed to discern hazards for human populations where ambient exposure levels are low, but the toxicologic hazards of these exposures remain high. The classes of agents under investigation include PAHs, heterocyclic aromatic amines (HAAs) associated with cooked foods, and aromatic amines. Serum albumin adducts of benzo[a]pyrene, B[a]P, one of the hydrocarbons, will be determined in human population studies using advanced HPLC-LIF methods to assess its role in human cancer. The structure of albumin adducts of PhIP, a prominent cooked-food carcinogen, will be determined and the adducts will be validated as exposure biomarkers. HPLC-LIF and MS methods for PhIP and aromatic amine DNA adducts will be developed and validated. Biomarker investigations of specific alkylanilines associated epidemiologically with bladder cancer will be undertaken to confirm their biological role.

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