“Stockpile” of Slight Transcriptomic Changes Determines the Indirect Genotoxicity of Low-Dose BPA in Thyroid Cells

• DOI: 10.1371/journal.pone.0151618
• Publication Date: 2016-03-16T20:15:53Z
• Authors: Immacolata Porreca; Luisa Ulloa Severino; Fulvio D’Angelo; Danila Cuomo; Michele Ceccarelli; Lucia Altucci; Elena Amendola; Angela Nebbioso; Massimo Mallardo; Mario De Felice; Concetta Ambrosino
• Keywords: DNA Replication; Pollutants; Time Factors; Time Factor; Benzhydryl Compounds; Cell Line; DNA Damage; DNA Replication; Dose-Response Relationship, Drug; Gene Expression; Humans; Phenols; Thyroid Gland; Time Factors; Transcriptome; Medicine (all); Biochemistry, Genetics and Molecular Biology (all); Agricultural and Biological Sciences (all); DNA rapair; Science; Thyroid Gland; Gene Expression; Cell Line; 03 medical and health sciences; thyroid, Genotoxicity, BPA; Phenols; Benzhydryl Compounds; Cell Line; DNA Damage; DNA Replication; Dose-Response Relationship, Drug; Gene Expression; Humans; Phenols; Thyroid Gland; Time Factors; Transcriptome; Agricultural and Biological Sciences (all); Biochemistry, Genetics and Molecular Biology (all); Medicine (all); Humans; DNA damage; DNA rapair; Thyroid; Pollutants; Benzhydryl Compounds; Benzhydryl Compound; Thyroid; 0303 health sciences; Biochemistry, Genetics and Molecular Biology (all); Phenol; Dose-Response Relationship, Drug; Medicine (all); Q; R; 3. Good health; Agricultural and Biological Sciences (all); DNA damage; Medicine; Transcriptome; Human; Research Article; DNA Damage

Epidemiological and experimental data highlighted the thyroid-disrupting activity of bisphenol A (BPA). Although pivotal to identify mechanisms toxicity, direct low-dose BPA effects on thyrocytes have not been assessed. Here, we report results microarray experiments revealing that transcriptome reacts dynamically exposure, adapting changes in gene expression exposure duration. The response involves many genes, enriching specific pathways biological functions mainly cell death/proliferation or DNA repair. Their is only slightly altered but, since they enrich pathways, this major as shown here for transcripts involved repair pathway. Indeed, even though no phenotypic are induced by treatment, show impairs further stressors. We experimentally verify prolonged low doses a delayed UV-C-induced damage, due impairment p21-Tp53 axis, with BPA-treated cells more prone death damage accumulation. present findings shed light possible mechanism which BPA, able directly cause genetic at environmental dose, may exert an indirect genotoxic activity.