title: PCB77 (3,3',4,4'-tetrachlorobiphenyl) co-exposure prolongs CYP1A induction, and sustains oxidative stress in B(a)P-exposed turbot, Scophthalmus maximus, in a long-term study.
abstract: Cytochrome P4501A (CYP1A), benzo(a)pyrene (B(a)P) activation and biliary elimination, phase II activities, and peroxisomal and antioxidant activities of turbot (Scophthalmus maximus) were studied in a long-term controlled experiment. Fish were serially exposed in water on day 1 and on completion of months 3, 6 and 9 to 0.1, 0.2, 0.1 and 0.1mg B(a)P/l, respectively, while another group was identically treated with additional PCB77 (3,3',4,4'-tetrachlorobiphenyl) at 1% of concomitant B(a)P (w/w). Temporally persistent responses were obtained by sampling on week 3 and 3 months from each latest exposure. Serial exposure to B(a)P+PCB77 progressively induced liver 7-ethoxyresorufin O-deethylase (EROD) activity and CYP1A protein levels (ELISA, western blotting) towards months 9, 12 and gill EROD activity on month 12. It associated with an apparent increase in liver benzo(a)pyrene diol epoxide (BPDE)-DNA adduct levels (ultrasensitive enzyme radioimmunoassay), and elevated bile B(a)P metabolite levels on month 9 females as compared to males. In contrast, B(a)P alone did not cause (p>0.05) comparable effects on liver EROD, CYP1A, adducts nor on bile metabolites. Both exposed groups demonstrated evidence for lasting oxidative stress as hepatic superoxide dismutase, catalase and glutathione peroxidase activities were significantly altered (p<0.05) with symptomatic pro-oxidant associations among them. Both treatments affected liver somatic index similarly (increase on month 3, decrease on month 9 in males). Continued exposure on month 18 (0.2mg B(a)P/l, 1% PCB77) followed by sampling 6 months later showed sustained induction (p<0.001) of hepatic EROD in B(a)P+PCB77 group, which was not seen in B(a)P alone treatment. Thus, PCB77 co-exposure prolonged CYP1A induction and contributed to a persistent oxidative challenge in B(a)P-exposed turbot. The results indicate synergistic effects of polycyclic aromatic hydrocarbon (PAH) and polychlorinated biphenyl (PCB) exposure in the aquatic environment.
authors.affiliation: Department of Molecular Biology, P.O. Box 7800, University of Bergen, HIB, N5020 Bergen, Norway. nandana.gunawickrama@gmail.com
authors.forename: S H N P
authors.initials: SH
authors.lastname: Gunawickrama
authors.forename: Niels
authors.initials: N
authors.lastname: Aarsaether
authors.forename: Amaia
authors.initials: A
authors.lastname: Orbea
authors.forename: Miren P
authors.initials: MP
authors.lastname: Cajaraville
authors.forename: Anders
authors.initials: A
authors.lastname: Goksøyr
mesh_terms: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001564:Benzo(a)pyrene / Q000493:pharmacokinetics / Q000633:toxicity*; D001646:Bile / Q000378:metabolism; D015153:Blotting, Western; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis* / Q000378:metabolism; D018736:DNA Adducts / Q000378:metabolism; D004357:Drug Synergism; D004790:Enzyme Induction; D005260:Female; D005412:Flatfishes / Q000254:growth & development / Q000378:metabolism; D005880:Gills / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D050217:Metabolic Detoxication, Phase II; D018384:Oxidative Stress / Q000187:drug effects*; D011078:Polychlorinated Biphenyls / Q000493:pharmacokinetics / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000493:pharmacokinetics / Q000633:toxicity*
chemical_list: D000975:Antioxidants; D018736:DNA Adducts; D014874:Water Pollutants, Chemical; C043931:benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA; D001564:Benzo(a)pyrene; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1; C028451:3,4,3',4'-tetrachlorobiphenyl