Binding of polycyclic aromatic hydrocarbons (PAHs) to teleost aryl hydrocarbon receptors (AHRs).
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous, environmental contaminants that pose a potential risk to fish populations. Both field and laboratory studies suggest that exposure of the early life stages of fish to PAH can mimic the embryotoxic effects of the planar halogenated hydrocarbons (PHHs), the most potent of which is 2,3,7,8-tetrachlorodibenzo-p-dioxin. PHH toxicity is mediated by the aryl hydrocarbon receptor (AHR) and PHH potency is predicted by its AHR-binding affinity and CYP1A induction potency. However, the role of the AHR, if any, in mediating the developmental effects of PAH to fish remains unknown. In this study we looked at the AHR binding affinity of a test set of PAH that had been previously ranked for their potency for inducing teleost CYP1A. PAH that induced CYP1A inhibited [3H]TCDD binding to in vitro-expressed AHRs from rainbow trout and the AHR expressed in PLHC-1 fish hepatoma cells. Generally, the relative rank order for AHR binding affinity predicted the rank order of these same PAH for inducing CYP1A reported in other studies. There was a strong, positive relationship between binding to the PLHC-1 AHR (stimulus) and the EC50s for CYP1A induction (response) in whole juvenile trout and in RTL-W1 cells, but EC50s were much higher than expected for a 1:1 stimulus/response relationship. These data show that the ability of PAH to bind to teleost AHR predicts PAH potency for CYP1A induction. If PAH toxicity is receptor-mediated and predicted by induction potencies, we will have a powerful mechanistic-based tool for rapidly assessing the risk of toxicity to fish of PAH from any source.
Billiard
Sonya M
SM
Department of Biology, Queen's University, ON, Kingston, Canada. sonyab@duke.edu
Hahn
Mark E
ME
Franks
Diana G
DG
Peterson
Richard E
RE
Bols
Niels C
NC
Hodson
Peter V
PV
D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis / Q000187:drug effects; D018076:DNA, Complementary / Q000235:genetics; D005399:Fishes / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D015386:Hazardous Substances / Q000378:metabolism / Q000494:pharmacology; D017686:Oncorhynchus mykiss; D010616:Phenanthrenes / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000378:metabolism; D011084:Polycyclic Aromatic Hydrocarbons / Q000378:metabolism* / Q000494:pharmacology; D011869:Radioligand Assay; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D015386:Hazardous Substances; D010616:Phenanthrenes; D000072317:Polychlorinated Dibenzodioxins; D011084:Polycyclic Aromatic Hydrocarbons; D018336:Receptors, Aryl Hydrocarbon; C447880:retene; D019363:Cytochrome P-450 CYP1A1