title: "Stockpile" of Slight Transcriptomic Changes Determines the Indirect Genotoxicity of Low-Dose BPA in Thyroid Cells.
abstract: Epidemiological and experimental data highlighted the thyroid-disrupting activity of bisphenol A (BPA). Although pivotal to identify the mechanisms of toxicity, direct low-dose BPA effects on thyrocytes have not been assessed. Here, we report the results of microarray experiments revealing that the transcriptome reacts dynamically to low-dose BPA exposure, adapting the changes in gene expression to the exposure duration. The response involves many genes, enriching specific pathways and biological functions mainly cell death/proliferation or DNA repair. Their expression is only slightly altered but, since they enrich specific pathways, this results in major effects as shown here for transcripts involved in the DNA repair pathway. Indeed, even though no phenotypic changes are induced by the treatment, we show that the exposure to BPA impairs the cell response to further stressors. We experimentally verify that prolonged exposure to low doses of BPA results in a delayed response to UV-C-induced DNA damage, due to impairment of p21-Tp53 axis, with the BPA-treated cells more prone to cell death and DNA damage accumulation. The present findings shed light on a possible mechanism by which BPA, not able to directly cause genetic damage at environmental dose, may exert an indirect genotoxic activity.
authors.affiliation: IRGS, Biogem, Via Camporeale, 83031, Ariano Irpino, Avellino, Italy.
authors.forename: Immacolata
authors.initials: I
authors.lastname: Porreca
authors.affiliation: University of Trieste, PhD School of Nanotechnology, Piazzale Europa 1, 34127, Trieste, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Ulloa Severino
authors.affiliation: IRGS, Biogem, Via Camporeale, 83031, Ariano Irpino, Avellino, Italy.
authors.forename: Fulvio
authors.initials: F
authors.lastname: D'Angelo
authors.affiliation: Department of Science and Technology, University of Sannio, Via Port'Arsa 11, 82100, Benevento, Italy.
authors.forename: Danila
authors.initials: D
authors.lastname: Cuomo
authors.affiliation: IRGS, Biogem, Via Camporeale, 83031, Ariano Irpino, Avellino, Italy.|Department of Science and Technology, University of Sannio, Via Port'Arsa 11, 82100, Benevento, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Ceccarelli
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Via L. De Crecchio 7, 80138, Napoli, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Altucci
authors.affiliation: Molecular Medicine and Medical Biotechnologies, University of Naples "Federico II", via Pansini 6, 80131, Napoli, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Amendola
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Via L. De Crecchio 7, 80138, Napoli, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Nebbioso
authors.affiliation: Molecular Medicine and Medical Biotechnologies, University of Naples "Federico II", via Pansini 6, 80131, Napoli, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Mallardo
authors.affiliation: Molecular Medicine and Medical Biotechnologies, University of Naples "Federico II", via Pansini 6, 80131, Napoli, Italy.|IEOS-CNR, Via Pansini 6, 80131 Napoli, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: De Felice
authors.affiliation: IRGS, Biogem, Via Camporeale, 83031, Ariano Irpino, Avellino, Italy.|Department of Science and Technology, University of Sannio, Via Port'Arsa 11, 82100, Benevento, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Ambrosino
mesh_terms: D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000633:toxicity*; D002460:Cell Line; D004249:DNA Damage; D004261:DNA Replication / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D010636:Phenols / Q000008:administration & dosage / Q000633:toxicity*; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D059467:Transcriptome; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds