Expression of P-glycoprotein and cytochrome p450 1A in intertidal fish (Anoplarchus purpurescens) exposed to environmental contaminants.

Whether P-glycoproteins (P-gps) like those which confer multidrug resistance in tumor cell lines are important in adaptation to chemicals in natural populations of vertebrates exposed to contaminant mixtures is the focus of this study. P-gp expression was examined in the intertidal fish high cockscomb blenny (Anoplarchus purpurescens) exposed to crude oil or pulp mill effluent. The relationship between P-gp expression and cytochrome p450 1A (CYP1A) induction also was investigated. Immunohistochemical (IHC) analysis revealed that levels of P-gp expression in the bile canaliculi were three- to five-fold greater in oil exposed fish than in control fish. Levels of P-gp expression were highly correlated with hepatic CYP1A levels previously measured in these fish. In fish from sites near pulp mills, P-gp expression in freshly caught fish did not correlate with proximity to pulp mills. However, hepatic P-gp expression levels in freshly caught fish were 14-fold higher than in fish from those sites that were depurated in clean water for 6 weeks. CYP1A levels were also elevated in liver of freshly caught as compared with depurated fish. Expression of neither CYP1A nor P-gp was elevated in depurated fish exposed to sediment and food from within the original pulp mill effluent stream. Depurated fish, which were injected with the aryl hydrocarbon receptor (AHR) agonist ss-naphthoflavone (BNF) showed an expected induction of CYP1A but no induction of P-gp. These results suggest that in blennies, unlike CYP1A, P-gp expression is not regulated by the AHR pathway; although P-gp and CYP1A both may be induced by some compounds in petroleum and unidentified xenobiotics at field sites. While our data indicate that CYP1A and P-gp are not coordinately regulated, these proteins may play complementary roles in cellular detoxification. Thus the elevation of P-gp activity may be an important mechanism of multixenobiotic resistance for organisms, such as intertidal fish, which are commonly exposed to anthropogenic contaminants and naturally occurring toxins.