title: Comparison of hepatic and extra hepatic induction of cytochrome P4501A by graded doses of aryl hydrocarbon receptor agonists in Atlantic tomcod from two populations.
abstract: Atlantic tomcod Microgadus tomcod from the Hudson River, New York, are exposed to high levels of polycyclic aromatic hydrocarbons (PAHs) and bioaccumulate mixtures of polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins and polychlorinatedfurans (PCDD/Fs). Previous studies demonstrated that hepatic cytochrome P4501A (CYP1A) mRNA was not inducible in tomcod from the Hudson River treated with single doses of PCB77 or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), but was inducible with PAHs. In this study, we sought to determine if CYP1A mRNA was inducible with higher doses of these and other halogenated aromatic hydrocarbons (HAHs) in Hudson River tomcod and if decreased sensitivity to gene inducibility occurs across all tissues. Tomcod from the Hudson River and the cleaner Miramichi River, New Brunswick, were treated individually with graded doses of TCDD and coplanar PCBs (PCB77, PCB81, PCB126, PCB169) and profiles of hepatic CYP1A mRNA expression were compared between the two populations. CYP1A mRNA inducibility was also compared in multiple tissues of tomcod from the two rivers that were treated with PCB77. Additionally, hepatic CYP1A mRNA was characterized in Miramichi River tomcod treated with pairs of PCB congeners that included aryl hydrocarbon receptor (AHR) agonists and antagonists. Hepatic CYP1A mRNA was significantly inducible by all agonists in tomcod from the Miramichi River and TCDD and two of four PCBs in tomcod from the Hudson River. CYP1A mRNA was also significantly inducible in four of five tissues of tomcod from the Miramichi River but only in liver of Hudson River tomcod. In summary, CYP1A mRNA inducibility was approximately two orders of magnitude less sensitive in tomcod from the Hudson River than in those from the Miramichi River. But when achieved, maximum levels of CYP1A expression were similar in tomcod from the two populations. Co-administration of PCB126 and PCB77 did not produce significantly greater CYP1A mRNA induction than administration of PCB126 alone and co-administration of mono-ortho-substituted PCB105 significantly decreased CYP1A mRNA inducibility by PCB77. These results indicate that CYP1A mRNA expression is significantly inducible by HAHs in tomcod from the Hudson River and suggest that all components of the AHR pathway are present and functional, but that the pathway is less sensitive to activation than in tomcod from the Miramichi River. Our results also indicate that CYP1A mRNA levels in environmentally exposed fish may not reflect additive tissue burdens of PCB congeners.
authors.affiliation: Department of Environmental Medicine, New York University School of Medicine, Tuxedo, 10987, USA.
authors.forename: Zhanpeng
authors.initials: Z
authors.lastname: Yuan
authors.forename: Simon
authors.initials: S
authors.lastname: Courtenay
authors.forename: Isaac
authors.initials: I
authors.lastname: Wirgin
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D004790:Enzyme Induction / Q000187:drug effects; D048388:Gadiformes; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D009509:New Brunswick; D009518:New York; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists* / Q000037:antagonists & inhibitors; D045483:Rivers; D014874:Water Pollutants, Chemical / Q000494:pharmacology*
chemical_list: D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D014874:Water Pollutants, Chemical; D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1; C027309:3,4,5,3',4',5'-hexachlorobiphenyl; C023035:3,4,5,3',4'-pentachlorobiphenyl; C028451:3,4,3',4'-tetrachlorobiphenyl