"Stockpile" of slight transcriptomic changes determines the indirect genotoxicity of low-dose BPA in thyroid cells

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

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17 Citations (Scopus)


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.

Original languageEnglish
Article numbere0151618
JournalPLoS One
Issue number3
Publication statusPublished - 1 Mar 2016
Externally publishedYes


ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Porreca, I., Ulloa Severino, L., D'Angelo, F., Cuomo, D., Ceccarelli, M., Altucci, L., Amendola, E., Nebbioso, A., Mallardo, M., De Felice, M., & Ambrosino, C. (2016). "Stockpile" of slight transcriptomic changes determines the indirect genotoxicity of low-dose BPA in thyroid cells. PLoS One, 11(3), [e0151618]. https://doi.org/10.1371/journal.pone.0151618