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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Enzyme-mediated dialdehyde formation: an alternative pathway for benzo[a]pyrene 7,8-dihydrodiol bioactivation.

Authors: Stansbury, K H; Noll, D M; Groopman, J D; Trush, M A

Published In Chem Res Toxicol, (2000 Nov)

Abstract: Polycyclic aromatic hydrocarbons, such as benzo[a]pyrene, are widespread environmental carcinogens of human concern. Several enzymatic systems have been shown to activate benzo[a]pyrene 7, 8-dihydrodiol, the proximate carcinogenic metabolite of benzo[a]pyrene, to a reactive species which produces both a chemiluminescence response and genotoxic lesions. The chemiluminescence response has been proposed to be the result of the formation of a dioxetane which upon ring opening forms a reactive dialdehyde intermediate. In in vitro incubations involving phorbol ester-stimulated human polymorphonuclear leukocytes or an isolated enzyme system consisting of myeloperoxidase, taurine, and hydrogen peroxide, a prolonged (>60 min) chemiluminescence response was observed from benzo[a]pyrene 7,8-dihydrodiol. HPLC analysis of the reaction mixture revealed the existence of a product which is dependent upon both taurine and the hydrocarbon. Characterization of this product using UV, NMR, and MS indicated that the product is a pyrene with two side chains resulting from bond breakage of a ring, yielding a dialdehyde. These side chains contain a portion of taurine covalently attached through imine formation with the aldehydes resulting from dioxetane ring opening. Replacement of taurine with either protein or DNA also produced a prolonged chemiluminescence response. These results demonstrate for the first time the formation of a novel electrophilic species from benzo[a]pyrene 7,8-dihydrodiol which along with an increased production of photons from this activation mechanism may lead to DNA and/or protein damage that is different from that elicited by diol epoxides.

PubMed ID: 11087440 Exiting the NIEHS site

MeSH Terms: Aldehydes/blood; Aldehydes/metabolism; Aldehydes/pharmacokinetics*; Biotransformation; Carcinogens, Environmental/pharmacokinetics*; Chromatography, High Pressure Liquid; Dihydroxydihydrobenzopyrenes/blood; Dihydroxydihydrobenzopyrenes/pharmacokinetics*; Heterocyclic Compounds/analysis; Heterocyclic Compounds/metabolism; Humans; Hydrogen Peroxide/metabolism; Hydrogen Peroxide/pharmacology; Luminescent Measurements; Mass Spectrometry; Neutrophils/enzymology; Neutrophils/metabolism; Nuclear Magnetic Resonance, Biomolecular; Peroxidase/metabolism*; Taurine/blood; Taurine/metabolism; Taurine/pharmacology

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