Widespread contamination of aquatic systems with
polycyclic aromatic hydrocarbons (PAHs) has led to concern about effects of PAHs on aquatic life. Some PAHs have been shown to cause
deformities in early life stages of fish that resemble those elicited by planar halogenated
aromatic hydrocarbons (pHAHs) that are agonists for the
aryl hydrocarbon receptor (AHR). Previous studies have suggested that activity of
cytochrome P4501A, a member of the AHR gene battery, is important to the toxicity of pHAHs, and inhibition of CYP1A can reduce the early-life-stage toxicity of pHAHs. In light of the effects of CYP1A inhibition on pHAH-derived toxicity, we explored the impact of both model and environmentally relevant CYP1A inhibitors on PAH-derived embryotoxicity. We exposed Fundulus heteroclitus embryos to two PAH-type AHR agonists, ss-naphthoflavone and
benzo(a)pyrene, and one pHAH-type AHR agonist, 3,3 ,4,4 ,5-pentachlorobiphenyl (PCB-126), alone and in combination with several CYP1A inhibitors. In agreement with previous studies, coexposure of embryos to
PCB-126 with the AHR antagonist and CYP1A inhibitor
alpha-naphthoflavone decreased frequency and severity of
deformities compared with embryos exposed to
PCB-126 alone. In contrast, embryos coexposed to the PAHs with each of the CYP1A inhibitors tested were deformed with increased severity and frequency compared with embryos dosed with PAH alone. The mechanism by which inhibition of CYP1A increased embryotoxicity of the PAHs tested is not understood, but these results may be helpful in elucidating mechanisms by which PAHs are embryotoxic. Additionally, these results call into question additive models of PAH embryotoxicity for environmental PAH mixtures that contain both AHR agonists and CYP1A inhibitors.