Page 551 - The Toxicology of Fishes

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Chemical Carcinogenesis in Fishes

Jeanette M. Rotchell, Michael R. Miller, David E. Hinton,
Richard T. Di Giulio, and Gary K. Ostrander

CONTENTS
Introduction............................................................................................................................................532
Historical Perspective ............................................................................................................................533
Early Discoveries .........................................................................................................................533
Association of Fish Cancers with Environmental Contaminants................................................534
Multistage Carcinogenesis.....................................................................................................................535
Classes of Chemical Carcinogens Investigated in Fishes.....................................................................537
Carcinogen Metabolism.........................................................................................................................539
AFB .............................................................................................................................................539
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DMBA ..........................................................................................................................................540
BaP ...............................................................................................................................................541
2-Acetylaminofluorene.................................................................................................................542
Carcinogen Alteration of DNA..............................................................................................................542
Specific Characterized Adducts ...................................................................................................542
AFB ....................................................................................................................................542
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DMBA.................................................................................................................................543
BaP......................................................................................................................................544
Oxidative DNA Damage ..............................................................................................................544
Chemical–Viral Interactions.........................................................................................................547
Epigenetic Carcinogens................................................................................................................548
DNA Repair ...........................................................................................................................................549
Overview of Repair Mechanisms.......................................................................................549
Direct Reversal (Pyrimidine Dimers).................................................................................549
Deficient/Low Excision Repair (Especially PAH Adducts)...............................................549
DNA Repair in Fish .....................................................................................................................550
AFB ....................................................................................................................................552
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DMBA and BaP..................................................................................................................552
Molecular Biology of Carcinogenesis...................................................................................................554
Oncogenes ....................................................................................................................................554
Classification of Oncogenes.........................................................................................................555
Class I Oncogenes: Receptor and Nonreceptor Protein Tyrosine Kinases ....................... 555
Class II Oncogenes: Growth Factors .................................................................................557
Class III Oncogenes: Receptors Lacking Protein Kinase Activity....................................557
Class IV Oncogenes: Membrane-Associated G Proteins ..................................................557
Class V Oncogenes: Cytoplasmic Protein Serine/Threonine Kinases............................... 558
Class VI Oncogenes: Cytoplasmic Regulators ..................................................................558
Class VII Oncogenes: Nuclear Transcription Regulators ..................................................558
Class VIII Oncogenes: Unclassified...................................................................................559

531