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 BPAtreated 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.

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 / S., De Flora; Micale, R. T.; S., La Maestra; A., Izzotti; F., D'Agostini; A., Camoirano; Davoli, Serena Alba; Troglio, Maria Giovanna; Rizzi, Federica Maria Angela; P., Davalli; Bettuzzi, Saverio. - In: TOXICOLOGICAL SCIENCES. - ISSN 1096-6080. - 122:(2011), pp. 45-51.

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

DAVOLI, Serena Alba;TROGLIO, Maria Giovanna;RIZZI, Federica Maria Angela;BETTUZZI, Saverio
2011-01-01

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 BPAtreated 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.
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 / S., De Flora; Micale, R. T.; S., La Maestra; A., Izzotti; F., D'Agostini; A., Camoirano; Davoli, Serena Alba; Troglio, Maria Giovanna; Rizzi, Federica Maria Angela; P., Davalli; Bettuzzi, Saverio. - In: TOXICOLOGICAL SCIENCES. - ISSN 1096-6080. - 122:(2011), pp. 45-51.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2370699
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 44
  • ???jsp.display-item.citation.isi??? 37
social impact