| Aryl hydrocarbons (AHs), including polycyclic AHs (PAHs) and halogenated AHs (HAHs), are ubiquitous environmental contaminants that cause an array of adverse effects which are believed to be mostly mediated by the aryl hydrocarbon receptor (AhR) pathway. The Hudson River (HR) is polluted with many HAHs, including polychlorinated-biphenyls (PCBs), -dibenzo-p-dioxins/-furans (PCDD/Fs) and PAHs, including benzo[a]pyrene (BaP).; Previous studies demonstrated that hepatic CYP1A1 mRNA was less inducible by 2,3,7,8-TCDD, but equally inducible by BaP, in adult tomcod from the HR compared to those from the cleaner Miramichi River (MR), NB. It is hypothesized that the HR tomcod population developed resistance, by genetic adaptation, to induction of CYP1A1 mRNA by HAHs due to chronic exposure to unusually high levels of HAHs in the HR.; Hepatic CYP1A1 mRNA levels in juvenile tomcod environmentally-exposed in the HR did not correlate with hepatic levels of HAHs, hepatic DNA adducts, or metabolites of PAHs, further suggesting that resistance to HAHs has developed in the HR population. In controlled laboratory experiments, CYP1A1 mRNA in hepatic and extra-hepatic tissues was less inducible by PCB77, PCB126 and PCB169, by two orders of magnitude, in HR than in MR tomcod, but was equally inducible by BaP. Early-life stages of tomcod from the HR and MR showed similar results as in adults, suggesting that genetic adaptation in the HR population was at least in part responsible for the observed resistance. Moreover, in laboratory challenge experiments, juvenile tomcod collected from sites spanning a large portion of the lower HR showed resistance to induction of CYP1A1 mRNA by PCB77, but not BaP, indicating that resistance is a population-wide phenomenon.; AhR polymorphisms among tomcod from the Hudson and three cleaner Canadian rivers were identified and characterized. An in-frame six-nucleotide sequence, encoding phenylalanine and leucine within the PAS C-terminal domain (PAC) of AhR, was deleted in HR tomcod. This variation may have resulted in structural changes in the PAC domain, as revealed by molecular computing, that are very likely to alter the function of AhR in HR tomcod and may be responsible for the resistance of HR tomcod to CYP1A1 mRNA induction by HAHs. |
