{
    "abstract": "Experimental evidence from the etiology of cancer studies suggests that a correlation between Bisphenol-A (BPA) exposure and alterations in hematopoiesis leads to blood cancer. In our study zebrafish were used to assess the lethality, developmental effect, embryonic apoptosis and changes in transcription factor of hematopoiesis through EGFR/ERK signaling pathways in response to BPA. The in silico interaction of EGFR and BPA was analysed by molecular dynamic simulation. According to our results, BPA induced a significant lethal effect in hatching retardation, reduction in heart rate and teratogenic effects on zebrafish embryos and larvae at three different concentrations 100, 500 and 2500 \u03bcg/L. The mortality of adult zebrafish exposed to the acute toxicity of BPA from 5 to 30 mg/L concentrations was determined for 96 h. The peripheral blood cells and vital organs such as kidney, liver and spleen from BPA exposed fish showed predominantly abnormal myeloid blast cells along with severe morphological changes in erythrocytes at sublethal concentration 245 \u03bcg/L. The BPA showed the highest binding affinity to zebrafish EGFR with a docking score of -7.5 kcal/mol with an RMSD of 3.0 nm during MD simulation. We found that EGFR/ERK overexpression leads to induce hematopoietic cell proliferation and impaired differentiation, which enhances the myeloid repopulating activity and the accumulation of immature myeloblast cells. BPA also caused a corresponding increase in expression of hematopoietic transcription factor c-MYB and RUNX-1 leading to polychromasia, poikilocytosis, acanthocytes and anisocytosis and promoted myeloblastosis by inhibiting GATA-1 expression. These morphological changes often resulted in the prior condition of acute myeloid leukemia (AML). Comprehensively, our data suggest that BPA can trigger the malignancy of AML cells by alteration of respective hematopoietic transcription factors via EGFR/ERK signaling in the zebrafish model.",
    "authors": [
        {
            "affiliation": "PG and Research Department of Zoology, Ayya Nadar Janaki Ammal College (Autonomous), Sivakasi 626124, Tamil Nadu, India; Cancer Biology Lab, Centre for Molecular and Nanomedical Sciences, Centre for Nanoscience and Nanotechnology, School of Bio and Chemical Engineering, Sathyabama Institute of Science and Technology, Chennai 600119, Tamil Nadu, India. Electronic address: sundarraj_sf529@anjaconline.org.",
            "firstname": "Shenbagamoorthy",
            "initials": "S",
            "lastname": "Sundarraj"
        },
        {
            "affiliation": "Cancer Biology Lab, Centre for Molecular and Nanomedical Sciences, Centre for Nanoscience and Nanotechnology, School of Bio and Chemical Engineering, Sathyabama Institute of Science and Technology, Chennai 600119, Tamil Nadu, India.",
            "firstname": "Mohanan V",
            "initials": "MV",
            "lastname": "Sujitha"
        },
        {
            "affiliation": "Cancer Biology Lab, Centre for Molecular and Nanomedical Sciences, Centre for Nanoscience and Nanotechnology, School of Bio and Chemical Engineering, Sathyabama Institute of Science and Technology, Chennai 600119, Tamil Nadu, India.",
            "firstname": "Carlton Ranjith Wilson",
            "initials": "CRW",
            "lastname": "Alphonse"
        },
        {
            "affiliation": "Cancer Biology Lab, Centre for Molecular and Nanomedical Sciences, Centre for Nanoscience and Nanotechnology, School of Bio and Chemical Engineering, Sathyabama Institute of Science and Technology, Chennai 600119, Tamil Nadu, India.",
            "firstname": "Retnamony",
            "initials": "R",
            "lastname": "Kalaiarasan"
        },
        {
            "affiliation": "Cancer Biology Lab, Centre for Molecular and Nanomedical Sciences, Centre for Nanoscience and Nanotechnology, School of Bio and Chemical Engineering, Sathyabama Institute of Science and Technology, Chennai 600119, Tamil Nadu, India. Electronic address: rajeshkannan.mnru@sathyabama.ac.in.",
            "firstname": "Rajaretinam Rajesh",
            "initials": "RR",
            "lastname": "Kannan"
        }
    ],
    "conclusions": null,
    "copyrights": "Copyright \u00a9 2021 Elsevier B.V. All rights reserved.",
    "doi": "10.1016/j.scitotenv.2021.147530",
    "journal": "The Science of the total environment",
    "keywords": [
        "Bisphenol-A",
        "Developmental effects",
        "EGFR/ERK signaling",
        "Hematopoiesis",
        "Myeloblastosis",
        "Zebrafish"
    ],
    "methods": null,
    "publication_date": "2021-05-19",
    "pubmed_id": "34004533",
    "results": null,
    "title": "Bisphenol-A alters hematopoiesis through EGFR/ERK signaling to induce myeloblastic condition in zebrafish model.",
    "xml": "<Element 'PubmedArticle' at 0x78850450c360>"
}