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Oncogenic Potential of Bisphenol A and Common Environmental Contaminants in Human Mammary Epithelial Cells

Authors
  • Nair, Vidhya A1
  • Valo, Satu2
  • Peltomäki, Päivi2
  • Bajbouj, Khuloud1
  • Abdel-Rahman, Wael M.1, 3
  • 1 (K.B.)
  • 2 (P.P.)
  • 3 Department of Medical Laboratory Sciences, College of Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, UAE
Type
Published Article
Journal
International Journal of Molecular Sciences
Publisher
MDPI AG
Publication Date
May 25, 2020
Volume
21
Issue
10
Identifiers
DOI: 10.3390/ijms21103735
PMID: 32466334
PMCID: PMC7279350
Source
PubMed Central
Keywords
License
Green

Abstract

There is an ample epidemiological evidence to support the role of environmental contaminants such as bisphenol A (BPA) in breast cancer development but the molecular mechanisms of their action are still not fully understood. Therefore, we sought to analyze the effects of three common contaminants (BPA; 4-tert-octylphenol, OP; hexabromocyclododecane, HBCD) on mammary epithelial cell (HME1) and MCF7 breast cancer cell line. We also supplied some data on methoxychlor, MXC; 4-nonylphenol, NP; and 2-amino-1-methyl-6-phenylimidazo [4–b] pyridine, PhIP. We focused on testing the prolonged (two months) exposure to low nano-molar concentrations (0.0015–0.0048 nM) presumed to be oncogenic and found that they induced DNA damage (evidenced by upregulation of pH2A.X, pCHK1, pCHK2, p-P53) and disrupted the cell cycle. Some agents induced epigenetic (methylation) changes of tumor suppressor genes TIMP3, CHFR, ESR1, IGSF4, CDH13, and GSTP1. Obviously, the accumulation of these molecular alterations is an essential base for cancer development. Consistent with this, we observed that these agents increased cellular invasiveness through collagen. Cellular abilities to form colonies in soft agar were increased for MCF7. Toxic agents induced phosphorylation of protein kinase such as EGFR, CREB, STAT6, c-Jun, STAT3, HSP6, HSP27, AMPKα1, FAK, p53, GSK-3α/β, and P70S6 in HME1. Most of these proteins are involved in potential oncogenic pathways. Overall, these data clarify the molecular alterations that can be induced by some common environmental contaminants in mammary epithelial cells which could be a foundation to understand environmental carcinogenesis.

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