Expression of multixenobiotic resistance transport P-glycoproteins in fish ( Fundulus heteroclitus) exposed to environmental xenobiotics

Abstract

P-glycoproteins (P-gps) are 170 kD transmembrane proteins that are efflux flippases preventing cellular accumulation of moderately hydrophobic compounds. In the liver, P-gps occur in bile canaliculi and transport endogenous and xenobiotic substrates. Proteins and genes related to P-gp occur in Fundulus heteroclitus (Cooper & Van Veld, personal communication). We examined hepatic P-gp expression via western blot in F. heteroclitus from a TCDD-resistant population from the New Bedford Harbor (NB) Superfund site, highly contaminated with planar halogenated aromatic hydrocarbons, and a reference population from Scorton Creek, Cape Cod (SC), a relatively unpolluted site. P-gp levels in SC field fish were two-fold higher than in NB field fish. Freshly collected fish from both sites had elevated P-gp levels compared to their respective cohorts that were depurated in clean aquaria for 44 days. P-gp levels in SC field fish were two-fold higher than in SC depurated fish. Depurated SC fish and field NB fish expressed similar P-gp levels, both of which were 30-fold higher than NB depurated fish. The basis for lower P-gp levels observed in NB field and depurated fish compared to SC fish is not known but could reflect differing exposure to natural products in sediment. Current studies are assessing P-gp inducing capacity of sedimentary material from SC and NB. Elevated hepatic P-gp levels in SC versus NB fish may contribute to their differing capacity to excrete xenobiotics, a difference suggested by studies of TCDD-exposed Fundulus (Bello & Hahn, personal communication). [Support: Howard Hughes Medical Institute and NIH ES-17381.]