title: Newspapers and newspaper ink contain agonists for the ah receptor.
abstract: Ligand-dependent activation of the aryl hydrocarbon receptor (AhR) pathway leads to a diverse array of biological and toxicological effects. The best-studied ligands for the AhR include polycyclic and halogenated aromatic hydrocarbons, the most potent of which is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, as new AhR ligands are identified and characterized, their structural and physiochemical diversity continues to expand. Our identification of AhR agonists in crude extracts from diverse materials raises questions as to the magnitude and extent of human exposure to AhR ligands through normal daily activities. We have found that solvent extracts of newspapers from countries around the world stimulate the AhR signaling pathway. AhR agonist activity was observed for dimethyl sulfoxide (DMSO), ethanol, and water extracts of printed newspaper, unprinted virgin paper, and black printing ink, where activation of luciferase reporter gene expression was transient, suggesting that the AhR active chemical(s) was metabolically labile. DMSO and ethanol extracts also stimulated AhR transformation and DNA binding, and also competed with [(3)H]TCDD for binding to the AhR. In addition, DMSO extracts of printed newspaper induced cytochrome P450 1A associated 7-ethoxyresorufin-O-deethylase activity in zebrafish embryos in vivo. Although the responsible bioactive chemical(s) remain to be identified, our results demonstrate that newspapers and printing ink contain relatively potent metabolically labile agonists of the AhR. Given the large amount of recycling and reprocessing of newspapers throughout the world, release of these easily extractable AhR agonists into the environment should be examined and their potential effects on aquatic organisms assessed.
authors.affiliation: Department of Environmental Toxicology, University of California, Davis, California 95616, USA.
authors.forename: Jessica E S
authors.initials: JE
authors.lastname: Bohonowych
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
authors.forename: Alicia
authors.initials: A
authors.lastname: Timme-Laragy
authors.forename: Dawoon
authors.initials: D
authors.lastname: Jung
authors.forename: Richard T
authors.initials: RT
authors.lastname: Di Giulio
authors.forename: Michael S
authors.initials: MS
authors.lastname: Denison
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D045424:Complex Mixtures / Q000737:chemistry / Q000633:toxicity*; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000201:enzymology; D004785:Environmental Pollutants / Q000737:chemistry / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D017930:Genes, Reporter / Q000187:drug effects; D006168:Guinea Pigs; D007281:Ink; D008024:Ligands; D008156:Luciferases / Q000235:genetics; D008297:Male; D009524:Newspapers as Topic; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D012997:Solvents / Q000737:chemistry; D015027:Zebrafish
chemical_list: D045424:Complex Mixtures; D004785:Environmental Pollutants; D008024:Ligands; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D012997:Solvents; D008156:Luciferases; D019363:Cytochrome P-450 CYP1A1