Bisphenol A induces DNA damage in cells exerting immune surveillance functions at peripheral and central level

Paola Di Pietro, Raffaella D'Auria, Andrea Viggiano, Elena Ciaglia, Rosaria Meccariello, Rossana Dello Russo, Annibale Alessandro Puca, Carmine Vecchione, Stefania Lucia Nori, Antonietta Santoro

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Abstract

Bisphenol A (BPA) is a synthetic xenoestrogen diffused worldwide. Humans are chronically exposed to low doses of BPA from food and drinks, thus BPA accumulates in tissues posing human health risk. In this study, we investigated the effects of BPA on peripheral blood mononuclear cells (PBMC) from human healthy donors, and in glia and microglia of rat offspring at postnatal day 17 (17PND) from pregnant females who received BPA soon after coupling and during lactation and weaning. Results indicated that BPA affected Phytoemagglutinin (PHA) stimulated PBMC proliferation causing an S-phase cell cycle accumulation at nanomolar concentrations while BPA was almost ineffective in resting PBMC. Furthermore, BPA induced chromosome aberrations and the appearance of shattered cells characterized by high number of fragmented and pulverized chromosomes, suggesting that the compound could cause a massive genomic rearrangement by inducing catastrophic events. The BPA-induced DNA damage was observed mainly in TCD4+ and TCD8+ subsets of T lymphocytes and was mediated by the increase of ERK1/2 phosphorylation, p21/Waf1 and PARP1 protein expression. Intriguingly, we observed for the first time that BPA-induced effects were associated to a sex specific modulation of ERα and ERβ in human PBMC. Immunofluorescence analysis of rat hippocampus corroborated in vitro findings showing that BPA induced ɣH2AX phosphorylation in microglia and astrocytosis by decreasing ERα expression within the dentate gyrus. Overall these results suggest that BPA can alter immune surveillance functions at both peripheral and central level with a potential risk for cancer, neuroinflammation and neurodegeneration.

Original languageEnglish
Pages (from-to)126819
JournalChemosphere
Volume254
DOIs
Publication statusPublished - Sep 2020

Keywords

  • Animals
  • Benzhydryl Compounds/toxicity
  • Cell Cycle
  • DNA Damage
  • Estrogen Receptor alpha/metabolism
  • Estrogen Receptor beta/metabolism
  • Female
  • Humans
  • Leukocytes, Mononuclear/drug effects
  • Male
  • Mitogen-Activated Protein Kinase 3
  • Phenols/toxicity
  • Phosphorylation
  • Pregnancy
  • Rats

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