Fundulus heteroclitus adapted to PAHs are cross-resistant to multiple insecticides

Atlantic killifish (Fundulus heteroclitus) from the Atlantic Wood Superfund site on the Elizabeth River (ER), VA are dramatically resistant to the acute toxicity and teratogenesis caused by polycyclic aromatic hydrocarbons (PAHs). To understand the consequences of adaptation to chronic PAH pollution, we have attempted to further define the chemical tolerance associated with this resistance. An important component of the PAH adaptation of ER fish is the dramatic down-regulation of the aryl hydrocarbon receptor (AHR) pathway, resulting in decreased cytochrome p450 (CYP) 1 activity. Herein, we compared the susceptibility to several insecticides of ER fish to that of reference site (King's Creek; KC) fish; use of these chemicals as probes of the resistance will help to demonstrate if the contaminant adaptation exhibited by ER fish is broad or narrow and AHR-focused. We hypothesized that ER fish would be less susceptible to the organophosphate chlorpyrifos (activated by CYP) and more susceptible to the pyrethroid permethrin (detoxified by CYP). Comparison of acute toxicity in 5-day-old larvae supported this hypothesis for chlorpyrifos. As expected, chemical up-regulation of CYP by co-exposure to β-naphthoflavone (BNF) enhanced the susceptibility of KC but it did not affect ER larvae. Unexpectedly, ER larvae were much less susceptible to permethrin than KC larvae. However, co-exposure to BNF greatly decreased the susceptibility of KC larvae, indicating that metabolism of permethrin by CYP was protective. Additionally, fish from each population were compared for susceptibility to the carbamate carbaryl, an acute neurotoxicant and weak AHR agonist that induces teratogenesis similar to that caused by PAHs. ER embryos and larvae were less susceptible than KC fish. These results suggest that the adaptive phenotype of ER fish is multi-faceted and that aspects other than CYP response are likely to greatly affect their response to contaminants.