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Int. J. Mol. Sci. 2015, 16(7), 14353-14368; doi:10.3390/ijms160714353

Atrazine Triggers DNA Damage Response and Induces DNA Double-Strand Breaks in MCF-10A Cells

1
Department of Agriculture & Environmental Sciences, Lincoln University of Missouri, Jefferson City, MO 65102, USA
2
Department of Pediatrics, Children's Mercy Hospitals and Clinics, University of Missouri Kansas City School of Medicine, Kansas City, MO 64108, USA
3
Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO 65211, USA
4
Division of Plant Sciences, University of Missouri, Columbia, MO 65211, USA
*
Authors to whom correspondence should be addressed.
Academic Editor: David Sheehan
Received: 17 March 2015 / Revised: 3 June 2015 / Accepted: 3 June 2015 / Published: 24 June 2015
(This article belongs to the Collection Advances in Proteomic Research)
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Abstract

Atrazine, a pre-emergent herbicide in the chloro-s-triazine family, has been widely used in crop lands and often detected in agriculture watersheds, which is considered as a potential threat to human health. Although atrazine and its metabolites showed an elevated incidence of mammary tumors in female Sprague–Dawley (SD) rats, no molecular evidence was found relevant to its carcinogenesis in humans. This study aims to determine whether atrazine could induce the expression of DNA damage response-related proteins in normal human breast epithelial cells (MCF-10A) and to examine the cytotoxicity of atrazine at a molecular level. Our results indicate that a short-term exposure of MCF-10A to an environmentally-detectable concentration of atrazine (0.1 µg/mL) significantly increased the expression of tumor necrosis factor receptor-1 (TNFR1) and phosphorylated Rad17 in the cells. Atrazine treatment increased H2AX phosphorylation (γH2AX) and the formation of γH2AX foci in the nuclei of MCF-10A cells. Atrazine also sequentially elevated DNA damage checkpoint proteins of ATM- and RAD3-related (ATR), ATRIP and phospho-Chk1, suggesting that atrazine could induce DNA double-strand breaks and trigger the DNA damage response ATR-Chk1 pathway in MCF-10A cells. Further investigations are needed to determine whether atrazine-triggered DNA double-strand breaks and DNA damage response ATR-Chk1 pathway occur in vivo. View Full-Text
Keywords: atrazine; DNA double-strand breaks; DNA damage response; MCF-10A cells atrazine; DNA double-strand breaks; DNA damage response; MCF-10A cells
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Huang, P.; Yang, J.; Ning, J.; Wang, M.; Song, Q. Atrazine Triggers DNA Damage Response and Induces DNA Double-Strand Breaks in MCF-10A Cells. Int. J. Mol. Sci. 2015, 16, 14353-14368.

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