Fluoranthene, but not benzo[a]pyrene, interacts with hypoxia resulting in pericardial effusion and lordosis in developing zebrafish.
Previous research has documented several PAHs that interact synergistically, causing severe teratogenicity in developing fish embryos. The coexposure of CYP1A inhibitors (e.g. FL or ANF) with AHR agonists (e.g. BaP or BNF) results in a synergistic increase in toxicity. As with chemical CYP1A inhibitors, it has also been shown that CYP1A morpholinos exacerbate BNF-induced embryotoxicity. We hypothesized that a hypoxia-induced reduction in CYP1A activity in BNF or BaP-exposed zebrafish embryos would similarly enhance pericardial effusion and other developmental abnormalities. BaP, BNF, ANF, and FL exposures, both individually and as BaP+FL or BNF+ANF combinations, were performed under hypoxia and normoxia. CYP1A activity in the BaP+hypoxia and BNF+hypoxia embryos was reduced by approximately 60% relative to normoxia embryos. Although CYP1A activity was significantly reduced, we did not observe any increase in pericardial effusion in either group. An unexpected yet particularly interesting result of these experiments was the observed interaction of both FL and ANF with hypoxia. Relatively high, yet environmentally relevant concentrations of FL (100-500 microg L(-1)) interact with moderate hypoxia (7.3% DO) through an unknown mechanism, resulting in pericardial effusion and severe lordosis. Additionally, ANF exposures (100 microg L(-1)) which are not normally teratogenic caused dramatic pericardial effusion, but not lordosis, when embryos were coexposed to hypoxia. These results suggest that reduced CYP1A activity may not exclusively underlie observed developmental toxicity, and that hypoxia may exacerbate the developmental toxicity of some PAH mixtures.
Nicholas School of the Environment, Duke University, Durham, NC 27708, United States.
Cole W
CW
Matson
Alicia R
AR
Timme-Laragy
Richard T
RT
Di Giulio
D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000187:drug effects* / Q000378:metabolism; D005449:Fluorenes / Q000633:toxicity*; D000860:Hypoxia / Q000503:physiopathology; D008141:Lordosis / Q000139:chemically induced* / Q000196:embryology; D010490:Pericardial Effusion / Q000139:chemically induced* / Q000196:embryology; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism; D029961:Zebrafish Proteins / Q000378:metabolism
D005449:Fluorenes; D029961:Zebrafish Proteins; D001564:Benzo(a)pyrene; C007738:fluoranthene; D019363:Cytochrome P-450 CYP1A1