title: Identification of lipidomic biomarkers for coexposure to subtoxic doses of benzo[a]pyrene and cadmium: the toxicological cascade biomarker approach.
abstract: The search for model bioassay systems indicating activation of different toxicological signaling pathways is one of the paramount goals of modern toxicology. Especially coexposure scenarios need to be investigated with respect to synergistic and interdependent effects for the activation of toxicological signaling pathways. The present study introduces an experimental in vitro model system for nontoxic and low-dose coexposures of human mammary carcinoma MCF-7 cells against polycyclic aromatic hydrocarbons (PAHs) such as benzo[a]pyrene (BP) and heavy metals such as cadmium. For the first time, a multivariate model that identifies 18 metabolic biomarkers has been shown to be sufficient to separate BP-treated cells from coexposed or control cells. A "toxicological pathway color code model" is introduced to visualize the results. Different biomarker subsets can be associated with specific HER2 signaling steps. A tiered cascade biomarker approach is proposed that could be used to identify profiles associated with tumorigenic potency of environmental toxicants in coexposure scenarios, including possible synergistic or additive effects.
authors.affiliation: Department of Product Safety, German Federal Institute for Risk Assessment (BfR) , Max-Dohrn-Strasse 8-10, 10589 Berlin, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Jungnickel
authors.forename: Sarah
authors.initials: S
authors.lastname: Potratz
authors.forename: Sven
authors.initials: S
authors.lastname: Baumann
authors.forename: Patrick
authors.initials: P
authors.lastname: Tarnow
authors.forename: Martin
authors.initials: M
authors.lastname: von Bergen
authors.forename: Andreas
authors.initials: A
authors.lastname: Luch
mesh_terms: D001564:Benzo(a)pyrene / Q000633:toxicity*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002104:Cadmium / Q000633:toxicity*; D063646:Carcinogenesis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D061986:MCF-7 Cells; D009362:Neoplasm Metastasis; D010713:Phosphatidylcholines / Q000096:biosynthesis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013109:Sphingomyelins / Q000096:biosynthesis
chemical_list: D001564:Benzo(a)pyrene; D014408:Biomarkers, Tumor; D002104:Cadmium; D010713:Phosphatidylcholines; D018719:Erb-b2 Receptor Tyrosine Kinases; D013109:Sphingomyelins; C508053:ERBB2 protein, human