| Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous, environmental contaminants that present a potential risk to fish populations. Both field and laboratory studies suggest that exposure of the early life stages (embryos and larvae) of fish to PAH can mimic the toxic effects of the planar halogenated hydrocarbons (PHHs), the most potent of which is 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD or dioxin). PHH toxicity for all vertebrates is thought to be mediated by the aryl hydrocarbon receptor (AHR) and is correlated with PHH potency for binding to the AHR and for inducing cytochrome P4501A (CYP1A) enzymes. Because PAH are ubiquitous, environmental contaminants, the risk of toxicity from chronic exposure to PAH may be greater. However, the role of the AHR, if any, in mediating the developmental effects of PAH to fish remains unknown.; Initial studies used the alkyl-substituted phenanthrene, retene, to model the toxicity of labile, non-carcinogenic PAH inducers because of its link to pulp and paper mills. Retene has been found in high concentrations in sediments downstream of some pulp mills and CYP1A induction has been observed in some fish populations downstream of these sites. CYP1A enzymes are also induced in juvenile trout exposed to retene. We observed that retene toxicity resembled that of TCDD to developing stages of fish and suggested that chronic exposure to PAH might be responsible for recruitment failure associated with pulp mill effluents and oil spills (Chapter 1).; Related experiments compared a test set of PAH using the dioxin model, which predicts that the toxicity of PAH to early life stages of fish should vary with PAH affinity for the AHR (Chapter 3) and with PAH potency for induction (Chapter 5). In Chapter 3, we showed that the rank order of PAH potency for inducing teleost CYP1A was the same rank order of these compounds for binding to teleost AHR. In Chapter 4, we showed that CYP1A induction in fish cell lines was a useful, cost-, and time-effective tool for predicting PAH exposure to live fish. The in vitro approach could also provide a rapid tool for assessing risk to early life stages if PAH toxicity varies with PAH potency for induction. This hypothesis, that potency for induction predicts potency for toxicity, was tested in Chapter 5.; PAH did not, however, show a rank order for toxicity as predicted from their induction potencies and relative AHR binding affinities. Unexpectedly, the non-inducer phenanthrene, and retene, the least potent inducer tested in this study, were the only PAH to be toxic to embryolarval stages of rainbow trout. High phenanthrene tissue concentrations in treated trout larvae suggest that dioxin-like toxicity was likely due to membrane damage via a narcotic mode of action. Alternatively, retene toxicity was consistent with oxidative stress mediated by the AHR. This has been also suggested as a possible toxic mechanism for dioxin effect. An increasing body of evidence suggests that the toxicity of alkyl-substituted PAH might be unique from that of unsubstituted PAH homologs and emphasizes the need for structure-activity models specific to this class of PAH. |
