Open Access

Genotoxicity of chloroacetamide herbicides and their metabolites in vitro and in vivo

  • Authors:
    • Xinyan Ma
    • Ying Zhang
    • Mingyang Guan
    • Weidong Zhang
    • Huifang Tian
    • Caixiao Jiang
    • Xiaoxin Tan
    • Weijun Kang
  • View Affiliations

  • Published online on: April 15, 2021     https://doi.org/10.3892/ijmm.2021.4936
  • Article Number: 103
  • Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The toxicity of chloroacetamide herbicide in embryo development remains unclear. Acetochlor (AC) is a chloroacetamide that metabolizes into 2‑ethyl‑6‑methyl-2-chloroacetanilide (CMEPA) and 6‑ethyl‑o‑toluidine (MEA). The present study determined the potential effect of AC and its metabolites on embryo development. Both HepG2 cells and zebrafish embryos were exposed to AC, CMEPA and MEA in the presence or absence of co‑treatment with anti‑reactive oxygen species (ROS) reagent N‑acetylcysteine. The generation of ROS, levels of superoxide dismutase (SOD) and glutathione (GSH) in HepG2 cells and lactate dehydrogenase (LDH) leakage from HepG2 cells were investigated. The effects of AC, CMEPA and MEA on DNA breakage, MAPK/ERK pathway activity, viability and apoptosis of HepG2 cells were examined by comet assay, western blotting, MTT assay and flow cytometry, respectively. Levels of LDH, SOD and GSH in zebrafish embryos exposed to AC, CMEPA and MEA were measured. The hatching and survival rates of zebrafish embryos exposed to AC, CMEPA and MEA, were determined, and apoptosis of hatched fish was investigated using acridine orange staining. The present data showed AC, CMEPA and MEA induced generation of ROS and decreased levels of SOD and GSH in HepG2 cells, which in turn promoted DNA breakage and LDH leakage from cells, ultimately inhibiting cell viability and inducing apoptosis, as well as phosphorylation of JNK and P38. However, co‑treatment with N‑acetylcysteine alleviated the pro‑apoptosis effect of AC and its metabolites. Moreover, exposure to AC, CMEPA and MEA lead to toxicity of zebrafish embryos with decreased SOD and GSH and increased LDH levels and cell apoptosis, ultimately decreasing the hatching and survival rates of zebrafish, all of which was attenuated by treatment with N‑acetylcysteine. Therefore, AC and its metabolites (CMEPA and MEA) showed cytotoxicity and embryo development toxicity.
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June-2021
Volume 47 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Ma X, Zhang Y, Guan M, Zhang W, Tian H, Jiang C, Tan X and Kang W: Genotoxicity of chloroacetamide herbicides and their metabolites <em>in vitro</em> and <em>in vivo</em>. Int J Mol Med 47: 103, 2021
APA
Ma, X., Zhang, Y., Guan, M., Zhang, W., Tian, H., Jiang, C. ... Kang, W. (2021). Genotoxicity of chloroacetamide herbicides and their metabolites <em>in vitro</em> and <em>in vivo</em>. International Journal of Molecular Medicine, 47, 103. https://doi.org/10.3892/ijmm.2021.4936
MLA
Ma, X., Zhang, Y., Guan, M., Zhang, W., Tian, H., Jiang, C., Tan, X., Kang, W."Genotoxicity of chloroacetamide herbicides and their metabolites <em>in vitro</em> and <em>in vivo</em>". International Journal of Molecular Medicine 47.6 (2021): 103.
Chicago
Ma, X., Zhang, Y., Guan, M., Zhang, W., Tian, H., Jiang, C., Tan, X., Kang, W."Genotoxicity of chloroacetamide herbicides and their metabolites <em>in vitro</em> and <em>in vivo</em>". International Journal of Molecular Medicine 47, no. 6 (2021): 103. https://doi.org/10.3892/ijmm.2021.4936