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

Autor: Stefania Lucia Nori, Andrea Viggiano, Elena Ciaglia, Antonietta Santoro, Rossana Dello Russo, Rosaria Meccariello, Annibale Alessandro Puca, Raffaella D'Auria, Paola Di Pietro, Carmine Vecchione
Rok vydání: 2020
Předmět:
Male
Health
Toxicology and Mutagenesis
0208 environmental biotechnology
02 engineering and technology
010501 environmental sciences
Hippocampus
01 natural sciences
chemistry.chemical_compound
Bisphenol A
Human lymphocytes
Pregnancy
Phosphorylation
Mitogen-Activated Protein Kinase 3
Microglia
Chemistry
Cell Cycle
Neurodegeneration
General Medicine
Cell cycle
Pollution
Xenoestrogen
medicine.anatomical_structure
Female
hormones
hormone substitutes
and hormone antagonists
endocrine system
medicine.medical_specialty
Environmental Engineering
DNA damage
Bisphenol A
Genotoxicity
Astrocytosis
Developmental neurotoxicity
Human lymphocytes
Hippocampus
Peripheral blood mononuclear cell
Phenols
Internal medicine
medicine
Animals
Estrogen Receptor beta
Humans
Environmental Chemistry
Benzhydryl Compounds
Neuroinflammation
0105 earth and related environmental sciences
urogenital system
Dentate gyrus
Estrogen Receptor alpha
Public Health
Environmental and Occupational Health
General Chemistry
medicine.disease
Rats
020801 environmental engineering
Astrocytosis
Endocrinology
Leukocytes
Mononuclear
Genotoxicity
Developmental neurotoxicity
DNA Damage
Zdroj: Chemosphere. 254:126819
ISSN: 0045-6535
DOI: 10.1016/j.chemosphere.2020.126819
Popis: 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.
Databáze: OpenAIRE
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