SYMPOSIA PAPER Published: 01 January 1996

Hepatic Cytochrome P450 1A as a Biomarker for Hydrocarbon and Oxidant Pollutants in Fish: Relevance of Identification of Specific Mechanism(s) of Induction and Potential Effects on Homeostasis


The induction of hepatic and extrahepatic P450 1A isozymes in fish and mammals is used as a biomarker for certain classes of toxic environmental pollutants, including polycyclic aromatic hydrocarbons (PAHs), planar polychlorinated (PCBs) and polybrominated (PBBs) biphenyl congeners, polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs). However, recent data from our laboratory have shown that rat pulmonary P450 1A1 can also be induced by arsenite or liver transplantation (via a stress mechanism), raising the possibility that regulation of this biomarker can occur by mechanisms other than Ah receptor-mediated increases of CYP1A gene transcription. To test this possibility a chimeric Ah receptor:estrogen receptor (AhRER) construct was prepared which was co-transfected with an estrogen response element-regulated luciferase reporter gene. Therefore, induction of luciferase activity demonstrates the presence of Ah receptor agonists in complex mixtures of environmental pollutants, and can be used to differentiate induction by receptor ligands and other mechanisms including oxidant stress/cytokine release. We also found that hepatic microsomes from two marine fish species and a marine mammal oxidize arachidonic acid (AA) to products which can function as potent intercellular and/or intracellular messengers, and that exposure to inducers of CYP1A significantly alters the AA metabolic profile. In concert, these observations raise the possibility that induction of P450 1A might interfere with homeostasis, particularly under conditions where significant amounts of free AA are released, as in oxidant stress.

Author Information

Zacharewski, TR
University of Western Ontario, London, Canada
McCallum, GP
University of Western Ontario, London, Canada
Stegeman, JJ
Woods Hole Oceanographic Institute, Woods Hole, MA
Bend, JR
University of Western Ontario, London, Canada
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Developed by Committee: E47
Pages: 165–187
DOI: 10.1520/STP15581S
ISBN-EB: 978-0-8031-5324-0
ISBN-13: 978-0-8031-1998-7