title: Atrazine Triggers DNA Damage Response and Induces DNA Double-Strand Breaks in MCF-10A Cells.
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.
authors.affiliation: Department of Agriculture & Environmental Sciences, Lincoln University of Missouri, Jefferson City, MO 65102, USA. phuang@cmh.edu.|Department of Pediatrics, Children's Mercy Hospitals and Clinics, University of Missouri Kansas City School of Medicine, Kansas City, MO 64108, USA. phuang@cmh.edu.
authors.forename: Peixin
authors.initials: P
authors.lastname: Huang
authors.affiliation: Department of Agriculture & Environmental Sciences, Lincoln University of Missouri, Jefferson City, MO 65102, USA. yangj@lincolnu.edu.
authors.forename: John
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO 65211, USA. jning@genome.wustl.edu.
authors.forename: Jie
authors.initials: J
authors.lastname: Ning
authors.affiliation: Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO 65211, USA. wangmx@missouri.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Wang
authors.affiliation: Division of Plant Sciences, University of Missouri, Columbia, MO 65211, USA. songq@missouri.edu.
authors.forename: Qisheng
authors.initials: Q
authors.lastname: Song
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D001280:Atrazine / Q000009:adverse effects / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D000071877:Checkpoint Kinase 1; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects; D006540:Herbicides / Q000009:adverse effects / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism
chemical_list: C521194:ATRIP protein, human; D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D006540:Herbicides; D006657:Histones; C113575:Rad17 protein, human; D047888:Receptors, Tumor Necrosis Factor, Type I; D011494:Protein Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1; C000605871:Chek1 protein, rat; D001280:Atrazine
keywords: DNA damage response; DNA double-strand breaks; MCF-10A cells; atrazine