Expression of P-glycoprotein in killifish (Fundulus heteroclitus) exposed to environmental xenobiotics

被引:42
作者
Bard, SM [1 ]
Bello, SM [1 ]
Hahn, ME [1 ]
Stegeman, JJ [1 ]
机构
[1] Woods Hole Oceanog Inst, Dept Biol, Woods Hole, MA 02543 USA
关键词
P-glycoprotein; multidrug resistance; multixenobiotic resistance; fish; aquatic environment; 2,3,7,8-tetrachlorodibenzofuran;
D O I
10.1016/S0166-445X(01)00256-9
中图分类号
Q17 [水生生物学];
学科分类号
071004 ;
摘要
P-glycoproteins (P-gp) are transmembrane efflux flippases that prevent the cellular accumulation of moderately hydrophobic compounds and are responsible for certain multidrug resistance phenotypes in tumor cell lines and human patients. We investigated whether P-gps could be involved in a contaminant resistant phenotype observed in a population of fish exposed over generations to high levels of planar halogenated aromatic hydrocarbons (PHAHs). Hepatic and intestinal epithelial P-gp expression was examined by immunoblot and immunohistochemistry in killifish (Fundulus heteroclitus) from New Bedford Harbor, MA (NBH), a Superfund site highly contaminated with PHAHs, and from Scorton Creek on Cape Cod, MA (SC), a relatively unpolluted site. The NBH population has developed resistance to the toxicity of PHAHs. Hepatic P-gp levels were more than 40% greater in fish freshly collected from SC than in fish freshly collected from NBH. When killifish from either site were maintained in clean water for up to 78 days to permit depuration of bioaccumulated contaminants, hepatic P-gp levels decreased approximately 50% by day 8. P-glycoprotein expression was detected in the intestinal epithelium in 55% of freshly collected NBH fish. However, depurated NBH fish and freshly caught and depurated SC fish rarely expressed P-gp in the intestine. In an effort to determine whether environmental chemicals at the two sites might contribute to altered P-gp expression, depurated fish were exposed either to sediment collected from SC or 2,3,7,8-tetrachlorodibenzofuran, a contaminant found at the NBH site and a model aryl hydrocarbon receptor agonist. Neither exposure affected hepatic P-gp levels in killifish. Elevated intestinal P-gp in NBH fish might counter the absorption of P-gp substrates/inducers and thus limit the amount of these compounds reaching the liver, which might account for the lower hepatic P-gp levels in NBH fish compared to SC fish. The differences in hepatic P-gp levels (SC > NBH) and intestinal P-gp (NBH > SC) in freshly collected fish also might reflect environmental exposure to different anthropogenic contaminants or microbial, algal, plant or other natural products via the water column, sediment, or diet at each site. (C) 2002 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:237 / 251
页数:15
相关论文
共 82 条
[1]  
Albertus JA, 2001, J EXP BIOL, V204, P217
[2]  
Bain LJ, 1996, TOXICOL APPL PHARM, V141, P288, DOI 10.1016/S0041-008X(96)80035-4
[3]   Multixenobiotic resistance as a cellular defense mechanism in aquatic organisms [J].
Bard, SM .
AQUATIC TOXICOLOGY, 2000, 48 (04) :357-389
[4]  
BARD SM, 2001, IN PRESS AQUAT TOXIC
[5]  
BARD SM, 2001, UNPUB CARCINOGENESIS
[6]   Acquired resistance to Ah receptor agonists in a population of Atlantic killifish (Fundulus heteroclitus) inhabiting a marine superfund site:: In vivo and in vitro studies on the inducibility of xenobiotic metabolizing enzymes [J].
Bello, SM ;
Franks, DG ;
Stegeman, JJ ;
Hahn, ME .
TOXICOLOGICAL SCIENCES, 2001, 60 (01) :77-91
[7]  
BELLO SM, 1999, BIOLOGY, P211
[8]   COINDUCTION OF MDR-1 MULTIDRUG-RESISTANCE AND CYTOCHROME-P-450 GENES IN RAT-LIVER BY XENOBIOTICS [J].
BURT, RK ;
THORGEIRSSON, SS .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1988, 80 (17) :1383-1386
[9]  
Chandwani S, 1992, Prog AIDS Pathol, V3, P65
[10]   INDUCTION OF MULTIDRUG RESISTANCE IN HUMAN-CELLS BY TRANSIENT EXPOSURE TO DIFFERENT CHEMOTHERAPEUTIC DRUGS [J].
CHAUDHARY, PM ;
RONINSON, IB .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1993, 85 (08) :632-639