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Polycyclic Aromatic Hydrocarbons: Chemistry and Carcinogenicity
Preface 1. Nomenclature 2. Environmental occurrence and cancer 3. Structure-activity relationships 4. Metabolic activation, DNA binding, and mechanisms of carcinogenesis 5. Molecular properties ofExpand
Benzo(a)pyrene diol epoxides as intermediates in nucleic acid binding in vitro and in vivo.
Evidence has been obtained that a specific isomer of a diol epoxide derivative of benzo(a)pyrene, (+/-)-7 beta,8alpha-dihydroxy-9alpha, 10alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene, is anExpand
Activation of Polycyclic Aromatic Hydrocarbontrans-Dihydrodiol Proximate Carcinogens by Human Aldo-keto Reductase (AKR1C) Enzymes and Their Functional Overexpression in Human Lung Carcinoma (A549)
The ability to measure DMBA-3,4-dione formation in A549 cells implicates the AKR pathway in the metabolic activation of PAH in human lung, and shows that four homogeneous human recombinant aldo-keto reductases (AKR1C1–AKR 1C4) are regioselective and oxidize only the relevant non-K regiontrans-dihydrodiols. Expand
Generation of reactive oxygen species during the enzymatic oxidation of polycyclic aromatic hydrocarbon trans-dihydrodiols catalyzed by dihydrodiol dehydrogenase.
The ability of DD to generate ROS during the oxidation of PAH trans-dihydrodiols (proximate carcinogens) may have important implications for tumor initiation and promotion. Expand
Metabolism of benzo[a]pyrene in human bronchoalveolar H358 cells using liquid chromatography-mass spectrometry.
This study shows that the P4501A1/1B1 and AKR pathways are inducible in human lung cells and that the peroxidase pathway was not, and provides evidence that each of the pathways of PAH activation yields their distinctive metabolites in H358 human lung Cells and that each pathway may contribute to the carcinogenic process. Expand
Formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dGuo) by PAH o-quinones: involvement of reactive oxygen species and copper(II)/copper(I) redox cycling.
Spectrophotometric assays showed that NADPH caused PAH o-quinones to enter futile redox cycles, which result in the depletion of excess cofactor, and that the immediate oxidant was not hydroxyl radical or Cu(I)OOH and that it is more likely (1)O(2), which can produce a 4,8-endoperoxide-dGuo intermediate. Expand
The ubiquitous aldehyde reductase (AKR1A1) oxidizes proximate carcinogen trans-dihydrodiols to o-quinones: potential role in polycyclic aromatic hydrocarbon activation.
The ability of this general metabolic enzyme to divert trans-dihydrodiols to o-quinones suggests that this pathway of PAH activation may be widespread in human tissues. Expand
Polycyclic Aromatic Hydrocarbons
From the Contents: Nomenclature and classification/ General chemistry/ Spectroscopy/ Chemical reactivity and theoretical predictability/ General synthetic methods (emphasis on new methods)/ AlternantExpand
Expression and characterization of four recombinant human dihydrodiol dehydrogenase isoforms: oxidation of trans-7, 8-dihydroxy-7,8-dihydrobenzo[a]pyrene to the activated o-quinone metabolite
Human liver possesses multiple AKRs which contribute to PAH activation by catalyzing the NADP+-dependent oxidation of PAH trans-dihydrodiols to redox-active o-quinones. Expand