PT  - JOURNAL ARTICLE
AU  - Madison C. Sestak
AU  - Julia A. Pinette
AU  - Caithlin M. Lamoureux
AU  - Susan L. Whittemore
TI  - Early Exposure to Polycyclic Aromatic Hydrocarbons (PAHs) and Cardiac Toxicity in a Species (<em>Xenopus laevis</em>) with Low Aryl Hydrocarbon Receptor (AHR) Responsiveness
AID  - 10.1101/301846
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 301846
4099  - http://biorxiv.org/content/early/2018/04/16/301846.short
4100  - http://biorxiv.org/content/early/2018/04/16/301846.full
AB  - Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous, persistent environmental contaminants, of which 16 are EPA-designated priority pollutants. Cardiotoxicity is observed in fish with developmental exposures to certain PAHs; however, the mechanism of toxicity can differ. Phenanthrene (PHE) and benzo(a)pyrene (BaP) are both cardiotoxic to fish, but PHE acts independently of aryl hydrocarbon receptor (AHR) activation while BaP-associated cardiotoxicity is AHR-dependent. To further understanding of mechanisms of toxicity, we compared the effects of early exposure to the priority PAHs pyrene (PYR), fluoranthene (FLA), PHE and BaP on cardiac function and cytochrome P450 type 1A (cyp1a) mRNA expression, an indicator of AHR activation, in a model system with lower AHR sensitivity than that of fish, the embryos and larvae of Xenopus laevis. Exposure to PYR, PHE, and FLA (0.25 – 25 μM) caused ventricular tachycardia early in heart development, but bradycardia and atrioventricular (AV) block in later stages. Elevated cyp1a mRNA levels indicate that FLA and BaP, but not PHE or PYR, are AHR agonists. The finding of FLA-induced cardiotoxicity and cyp1a expression (35-fold) is particularly surprising as FLA inhibits CYP1A activity in fish and, as a single compound, is not cardiotoxic. Our results suggest that early exposure to PHE, PYR, and FLA, but not to BaP, compromises cardiac function by altering normal pacemaker activity and conduction in Xenopus, effects associated with increased mortality. Our findings also reveal a considerable degree of species specificity between fish and frog regarding cardiac sensitivity to developmental PAH exposures and have implications for the cardiovascular health of PAH-exposed humans and wild amphibians.