title: Constitutive expression of the AHR signaling pathway in a bovine mammary epithelial cell line and modulation by dioxin-like PCB and other AHR ligands.
abstract: Environmental pollutants, such as dioxin-like (DL) PCBs, benzo(a) pyrene (B[a]P), and flavonoids are aryl hydrocarbon receptor (AHR) ligands and may be excreted in dairy milk. The expression of AHR-target genes, particularly those involved in xenobiotic biotransformation, and their modulation by two DL-PCBs, B[a]P, and β-naphthoflavone was investigated in a bovine mammary epithelial cell line (BME-UV). As assessed by quantitative PCR, BME-UV cells expressed a functional AHR signaling pathway. All the AHR ligands induced a concentration-related increase in the transcription of cytochrome P450 1A1 and 1B1, known to be implicated in the bioactivation of several xenobiotics. Conversely, genes encoding for antioxidant and detoxifying enzymes, like quinone oxidoreductase or glutathione S-transferase A2, were not affected or even depressed. This study demonstrates the occurrence and the modulation by different AHR-ligands of genes involved in xenobiotic metabolism in BME-UV cells, with the potential generation of (re) active metabolites that may damage mammary tissue and/or affect animal or human health via the contaminated milk.
authors.affiliation: Department of Veterinary Sciences, University of Torino, Largo Braccini 2, Grugliasco, Italy. Electronic address: flavia.girolami@unito.it.
authors.forename: Flavia
authors.initials: F
authors.lastname: Girolami
authors.affiliation: Department of Veterinary Sciences, University of Torino, Largo Braccini 2, Grugliasco, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Spalenza
authors.affiliation: Department of Veterinary Sciences, University of Torino, Largo Braccini 2, Grugliasco, Italy.
authors.forename: Livio
authors.initials: L
authors.lastname: Manzini
authors.affiliation: Department of Veterinary Sciences, University of Torino, Largo Braccini 2, Grugliasco, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Carletti
authors.affiliation: Department of Veterinary Sciences, University of Torino, Largo Braccini 2, Grugliasco, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Nebbia
mesh_terms: D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D002417:Cattle; D002460:Cell Line; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis / Q000235:genetics; D065633:Cytochrome P-450 CYP1B1 / Q000096:biosynthesis / Q000235:genetics; D015536:Down-Regulation; D004785:Environmental Pollutants / Q000633:toxicity*; D004790:Enzyme Induction; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D019324:beta-Naphthoflavone / Q000633:toxicity*
chemical_list: D004785:Environmental Pollutants; D007527:Isoenzymes; D008024:Ligands; D018336:Receptors, Aryl Hydrocarbon; D001564:Benzo(a)pyrene; D019324:beta-Naphthoflavone; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D005982:Glutathione Transferase; C119995:glutathione S-transferase alpha
keywords: AHR-agonist; Bovine mammary epithelial cell; Dioxin-like PCB; Gene expression; Xenobiotic metabolizing enzyme