title: Complex interactions between dioxin-like and non-dioxin-like compounds for in vitro cellular responses: implications for the identification of dioxin exposure biomarkers.
abstract: Despite considerable advances in reducing the production of dioxin-like toxicants in recent years, contamination of the food chain still occasionally occurs resulting in huge losses to the agri-food sector and risk to human health through exposure. Dioxin-like toxicity is exhibited by a range of stable and bioaccumulative compounds including polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), produced by certain types of combustion, and man-made coplanar polychlorinated biphenyls (PCBs), as found in electrical transformer oils. While dioxinergic compounds act by a common mode of action making exposure detection biomarker based techniques a potentially useful tool, the influence of co-contaminating toxicants on such approaches needs to be considered. To assess the impact of possible interactions, the biological responses of H4IIE cells to challenge by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in combination with PCB-52 and benzo-a-pyrene (BaP) were evaluated by a number of methods in this study. Ethoxyresorufin-O-deethylase (EROD) induction in TCDD exposed cells was suppressed by increasing concentrations of PCB-52, PCB-153, or BaP up to 10 μM. BaP levels below 1 μM suppressed TCDD stimulated EROD induction, but at higher concentrations, EROD induction was greater than the maximum observed when cells were treated with TCDD alone. A similar biphasic interaction of BaP with TCDD co-exposure was noted in the AlamarBlue assay and to a lesser extent with PCB-52. Surface enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF) profiling of peptidomic responses of cells exposed to compound combinations was compared. Cells co-exposed to TCDD in the presence of BaP or PCB-52 produced the most differentiated spectra with a substantial number of non-additive interactions observed. These findings suggest that interactions between dioxin and other toxicants create novel, additive, and non-additive effects, which may be more indicative of the types of responses seen in exposed animals than those of single exposures to the individual compounds.
authors.affiliation: Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast , David Keir Building Stranmillis Road, Belfast BT9 5AG, Ireland.
authors.forename: Anthony A
authors.initials: AA
authors.lastname: O'Kane
authors.forename: Chris T
authors.initials: CT
authors.lastname: Elliott
authors.forename: Mark H
authors.initials: MH
authors.lastname: Mooney
mesh_terms: D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D015415:Biomarkers; D045744:Cell Line, Tumor; D002470:Cell Survival; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D010078:Oxazines / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D051381:Rats; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014966:Xanthenes / Q000378:metabolism
chemical_list: D015415:Biomarkers; D004785:Environmental Pollutants; D010078:Oxazines; D000072317:Polychlorinated Dibenzodioxins; D014966:Xanthenes; C009407:2,5,2',5'-tetrachlorobiphenyl; C005843:resazurin; D001564:Benzo(a)pyrene; D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1