Upregulation of clusterin in prostate and DNA damage in spermatozoa from bisphenol A-treated rats and formation of DNA adducts in cultured human prostatic cells

Autor: Sebastiano La Maestra, Serena Davoli, Federica Rizzi, Saverio Bettuzzi, Pierpaola Davalli, Anna Camoirano, Rosanna T. Micale, Alberto Izzotti, Silvio De Flora, Maria Giovanna Troglio, Francesco D'Agostini
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Male
analysis
clusterin
bisphenol A
genetics/metabolism
chemically induced/pathology
Toxicology
Rats
Sprague-Dawley
chemistry.chemical_compound
DNA Adducts
Prostate
Single-Stranded
DNA adducts
Sprague Dawley rats
prostate
spermatozoa
Blotting
analysis/metabolism
cytology/metabolism/pathology
Spermatozoa
Up-Regulation
Xenoestrogen
medicine.anatomical_structure
Liver
DNA fragmentation
Biological Markers
Comet Assay
Drug
Western
hormones
hormone substitutes
and hormone antagonists
endocrine system
DNA damage
Blotting
Western
DNA Fragmentation
Biology
Thiobarbituric Acid Reactive Substances
Cell Line
Dose-Response Relationship
Phenols
medicine
Animals
Humans
DNA Breaks
Single-Stranded
Benzhydryl Compounds
Clusterin
Dose-Response Relationship
Drug
urogenital system
drug effects/pathology
DNA Breaks
toxicity
Prostatic Neoplasms
Epithelial Cells
Animals
Biological Markers
analysis
Blotting
Western
Cell Line
Clusterin
genetics/metabolism
Comet Assay
DNA Adducts
drug effects
DNA Breaks
drug effects
DNA Fragmentation
drug effects
Dose-Response Relationship
Drug
Epithelial Cells
cytology
Humans
Liver
cytology
Male
Phenols
toxicity
Prostate
cytology/metabolism/pathology
Prostatic Neoplasms
chemically induced/pathology
Rats
Rats
Sprague-Dawley
Reactive Oxygen Species
analysis/metabolism
Spermatozoa
drug effects/pathology
Thiobarbituric Acid Reactive Substances
analysis/metabolism
Up-Regulation
drug effects
Rats
Comet assay
chemistry
Apoptosis
Cell culture
Immunology
Cancer research
biology.protein
cytology
Sprague-Dawley
Reactive Oxygen Species
Biomarkers
Popis: Among endocrine disruptors, the xenoestrogen bisphenol A (BPA) deserves particular attention due to widespread human exposure. Besides hormonal effects, BPA has been suspected to be involved in breast and prostate carcinogenesis, which share similar estrogen-related mechanisms. We previously demonstrated that administration of BPA to female mice results in the formation of DNA adducts and proteome alterations in the mammary tissue. Here, we evaluated the ability of BPA, given with drinking water, to induce a variety of biomarker alterations in male Sprague-Dawley rats. In addition, we investigated the formation of DNA adducts in human prostate cell lines. In BPA-treated rats, no DNA damage occurred in surrogate cells including peripheral blood lymphocytes and bone marrow erythrocytes, where no increase of single-strand DNA breaks was detectable by comet assay and the frequency of micronucleated cells was unaffected by BPA. Liver cells were positive at transferase dUTP nick end labeling assay, which detects both single-strand and double-strand breaks and early stage apoptosis. BPA upregulated clusterin expression in atrophic prostate epithelial cells and induced lipid peroxidation and DNA fragmentation in spermatozoa. Significant levels of DNA adducts were formed in prostate cell lines treated either with high-dose BPA for 24 h or low-dose BPA for 2 months. The BPA-related increase of DNA adducts was more pronounced in PNT1a nontumorigenic epithelial cells than in PC3 metastatic carcinoma cells. On the whole, these experimental findings support mechanistically the hypothesis that BPA may play a role in prostate carcinogenesis and may, potentially, affect the quality of sperm.
Databáze: OpenAIRE
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