title: 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.
abstract: 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.
authors.affiliation: Department of Health Sciences, University of Genoa, Genoa, Italy. sdf@unige.it
authors.forename: Silvio
authors.initials: S
authors.lastname: De Flora
authors.forename: Rosanna T
authors.initials: RT
authors.lastname: Micale
authors.forename: Sebastiano
authors.initials: S
authors.lastname: La Maestra
authors.forename: Alberto
authors.initials: A
authors.lastname: Izzotti
authors.forename: Francesco
authors.initials: F
authors.lastname: D'Agostini
authors.forename: Anna
authors.initials: A
authors.lastname: Camoirano
authors.forename: Serena A
authors.initials: SA
authors.lastname: Davoli
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Troglio
authors.forename: Federica
authors.initials: F
authors.lastname: Rizzi
authors.forename: Pierpaola
authors.initials: P
authors.lastname: Davalli
authors.forename: Saverio
authors.initials: S
authors.lastname: Bettuzzi
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D002460:Cell Line; D051152:Clusterin / Q000235:genetics / Q000378:metabolism*; D020552:Comet Assay; D018736:DNA Adducts / Q000187:drug effects; D053904:DNA Breaks, Single-Stranded / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology; D006801:Humans; D008099:Liver / Q000166:cytology; D008297:Male; D010636:Phenols / Q000633:toxicity*; D011467:Prostate / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000139:chemically induced / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism; D013094:Spermatozoa / Q000187:drug effects* / Q000473:pathology; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D015415:Biomarkers; D051152:Clusterin; D018736:DNA Adducts; D010636:Phenols; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; C006780:bisphenol A; D000098826:Bisphenol A Compounds