title: Gene expression and metabolic responses of HepG2/C3A cells exposed to flame retardants and dust extracts at concentrations relevant to indoor environmental exposures.
abstract: Humans are routinely exposed to mixtures of flame retardants (FRs) from multiple sources including indoor dust. As a model to explore the potential effects of FR exposure from indoor dust on human health, the molecular responses of human hepatoma cells (HepG2/C3A cells) to a defined mixture of FRs and to a dust extract were investigated using multiple non-targeted omics approaches. A solvent extract of an indoor dust standard reference material SRM2585 was used as the surrogate dust sample, while a mixture of four FRs (TCEP, TCIPP, TDCIPP and HBCD) was used to mimic the FR mixture in the indoor dust. Cytotoxicity tests indicated there were no significant changes to cell viability or cell integrity after a 24- or 72-h exposure of HepG2/C3A cells to the FR mixture or to the dust extract. However, transcriptomics revealed changes in gene expression associated with the metabolism of xenobiotics (e.g. CYP1A1, CYP1A2, CYP2B6) in the dust extract group but not in the FR mixture group after a 72-h exposure. Few metabolic or lipidomic changes were detected in response to either the FR mixture or to the dust extract group. Given that the dust extract contained components that elicited a biological response, in contrast to the lack of response induced by the FR mixture, our findings suggest that the most likely causes of the molecular responses to indoor dust exposure lie in components other than the four FRs investigated, e.g. caused by PAHs or PCBs.
authors.affiliation: School of Biosciences, University of Birmingham, Birmingham, B15 2TT, UK.
authors.forename: Jinkang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Geography, Earth & Environmental Sciences, University of Birmingham, Birmingham, B15 2TT, UK; Department of Analytical Chemistry, Faculty of Pharmacy, Assiut University, 71526, Assiut, Egypt.
authors.forename: Mohamed Abou-Elwafa
authors.initials: MA
authors.lastname: Abdallah
authors.affiliation: School of Biosciences, University of Birmingham, Birmingham, B15 2TT, UK.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Williams
authors.affiliation: School of Geography, Earth & Environmental Sciences, University of Birmingham, Birmingham, B15 2TT, UK.
authors.forename: Stuart
authors.initials: S
authors.lastname: Harrad
authors.affiliation: School of Biosciences, University of Birmingham, Birmingham, B15 2TT, UK.
authors.forename: James K
authors.initials: JK
authors.lastname: Chipman
authors.affiliation: School of Biosciences, University of Birmingham, Birmingham, B15 2TT, UK. Electronic address: M.Viant@bham.ac.uk.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Viant
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D016902:Air Pollution, Indoor / Q000009:adverse effects; D045744:Cell Line, Tumor; D004391:Dust; D004781:Environmental Exposure / Q000009:adverse effects; D005411:Flame Retardants / Q000633:toxicity*; D020869:Gene Expression Profiling; D006801:Humans; D055432:Metabolomics
chemical_list: D000393:Air Pollutants; D004391:Dust; D005411:Flame Retardants
keywords: DIMS; Flame retardant mixture; Indoor dust; Microarray