TP5 Mechanisms of Toxic Action
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1:20 PM - 4:40 PM, Tuesday
() Aryl hydrocarbon receptor-dependent and –independent pathways of polycyclic aromatic hydrocarbon toxicity in fish embryos.
Incardona, J1, Carls, M2, Teraoka, H.3, Collier, T1, Scholz, N1, 1 NOAA Northwest Fisheries Science Center, Seattle, WA, USA2 NOAA Auke Bay Laboratory, Juneau, AK, USA3 Rakuno Gakuen University, Ebetsu, Japan
ABSTRACT- Exposure of fish embryos to complex mixtures of polycyclic aromatic hydrocarbons (PAHs), such as weathered crude oil, results in a syndrome of cardiovascular dysfunction, edema, craniofacial and body axis defects. Using zebrafish (Danio rerio) we analyzed the effects of individual PAH compounds containing 2-4 rings, representing the homologous series typically abundant in weathered oil. Individual compounds produced distinct defects in zebrafish embryos: compounds containing three rings (dibenzothiophene and phenanthrene) caused cardiac dysfunction relatively early in development (30-36 hours post-fertilization [hpf]), which resulted in downstream effects of edema and craniofacial and body axis defects. Blockade of the aryl hydrocarbon receptor (AhR) pathway by injection of an AhR antisense morpholino oligonucleotide inhibited vascular cytochrome P4501A (CYP1A) induction by phenanthrene, but failed to inhibit phenanthrene-induced cardiac dysfunction. In contrast, exposure to the 4-ring compound pyrene resulted in peripheral vascular defects, mild pericardial edema, and neural tube cell death later in development (96 hpf). These effects of pyrene were blocked by AhR morpholino injection, as was pyrene-induced CYP1A expression in the vasculature and liver. These findings indicate that 4-ring PAHs (e.g. pyrene) act through mechanisms that require the AhR pathway, while 3-ring PAHs (e.g. phenanthrene) most likely act directly on the heart by an AhR-independent mechanism. Exposure of zebrafish embryos to weathered crude oil by two methods (static water-accommodated fraction and continuous flow oiled-rock column) resulted in cardiac dysfunction by 30-36 hpf. However, additional abnormalities were observed by 54 hpf that did not occur with individual model PAHs, including intracranial hemorrhage and fin fold defects. The contribution of AhR-dependent and –independent mechanisms to these phenotypes was analyzed by antisense morpholino blockade of the AhR pathway.
Key words: fish development, petroleum