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Article

Dimethoate Induces DNA Damage and Mitochondrial Dysfunction Triggering Apoptosis in Rat Bone-Marrow and Peripheral Blood Cells

1
Gene-Tox Laboratory, Division of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh 202002, UP, India
2
Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, J&K, India
3
Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia
4
Medical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC), Riyadh 3660, Saudi Arabia
5
Ministry of National Guard—Health Affairs (MNGHA), King Saud bin Abdulaziz University for Health Sciences, Riyadh 22490, Saudi Arabia
6
Department of Biology, College of Science, University of Ha’il, Hail 2440, Saudi Arabia
7
Center of Excellence in Genomic Medicine Research (CEGMR), King Fahad Medical Research Centre, KAU, Jeddah 21589, Saudi Arabia
*
Author to whom correspondence should be addressed.
Toxics 2020, 8(4), 80; https://doi.org/10.3390/toxics8040080
Received: 1 September 2020 / Revised: 26 September 2020 / Accepted: 28 September 2020 / Published: 1 October 2020
(This article belongs to the Special Issue Environmental and Human Health Risk Assessment of POPs)
Dimethoate (DM) is an organophosphorus (OP) pesticide with wide use in the pest control. Its persistence in crops and soils could possibly cause adverse health consequences in humans as well as other non-target species. Since molecular studies confirming potential genotoxicity of DM have not been previously reported, the acute in vivo toxicological impact was evaluated in Wistar rats. Significant micronuclei induction and metaphase chromosome abnormalities in bone marrow cells exposed to three different DM doses (20, 40 and 60 mg/kg-bw) at multiple treatment durations (24, 48 and 72 h) indicated positive dose response relationship, confirming its genotoxic and cytotoxic potential. Significant mitotic index decrease was seen in dosed animals compared to vehicle control. The study used peripheral blood comet assay, indicating DM-mediated damage to DNA at all exposure levels in a time responsive manner. These assays were found to be an effective, precise, and fast technique with applied value in biomonitoring studies. Cell cycle and apoptosis along with mitochondrial membrane potential (MMP) in flow cytometric analyses confirmed DM exposure decreased MMP, affected the cell cycle, and inflicted DNA damage, which led to cellular apoptosis of leukocytes culminating into immunotoxic effects. The in silico experiments consequently augmented that DM showed acceptable binding energy value for Cyclin A2, suggesting that it could inhibit the cell cycle progression by inhibiting cyclin A2. View Full-Text
Keywords: Dimethoate; comet assay; genotoxicity; cell cycle; mitochondrial membrane potential Dimethoate; comet assay; genotoxicity; cell cycle; mitochondrial membrane potential
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MDPI and ACS Style

Nazam, N.; Lone, M.I.; Hamid, A.; Qadah, T.; Banjar, A.; Alam, Q.; Saeed, M.; Ahmad, W. Dimethoate Induces DNA Damage and Mitochondrial Dysfunction Triggering Apoptosis in Rat Bone-Marrow and Peripheral Blood Cells. Toxics 2020, 8, 80. https://doi.org/10.3390/toxics8040080

AMA Style

Nazam N, Lone MI, Hamid A, Qadah T, Banjar A, Alam Q, Saeed M, Ahmad W. Dimethoate Induces DNA Damage and Mitochondrial Dysfunction Triggering Apoptosis in Rat Bone-Marrow and Peripheral Blood Cells. Toxics. 2020; 8(4):80. https://doi.org/10.3390/toxics8040080

Chicago/Turabian Style

Nazam, Nazia, Mohammad I. Lone, Abid Hamid, Talal Qadah, Alaa Banjar, Qamre Alam, Mohd Saeed, and Waseem Ahmad. 2020. "Dimethoate Induces DNA Damage and Mitochondrial Dysfunction Triggering Apoptosis in Rat Bone-Marrow and Peripheral Blood Cells" Toxics 8, no. 4: 80. https://doi.org/10.3390/toxics8040080

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