Format

Send to

Choose Destination
Chemosphere. 2020 Mar;243:125345. doi: 10.1016/j.chemosphere.2019.125345. Epub 2019 Nov 9.

Toxicity assessment of the herbicide acetochlor in the human liver carcinoma (HepG2) cell line.

Author information

1
State Environmental Protection Key Laboratory of Wetland Ecology and Vegetation Restoration, School of Environment, Northeast Normal University, Changchun, Jilin, 130117, PR China.
2
State Environmental Protection Key Laboratory of Wetland Ecology and Vegetation Restoration, School of Environment, Northeast Normal University, Changchun, Jilin, 130117, PR China. Electronic address: zhaoyh@nenu.edu.cn.
3
Center for Environmental and Human Toxicology, Department of Physiological Sciences, College of Veterinary Medicine, UF Genetics Institute, Interdisciplinary Program in Biomedical Sciences Neuroscience, University of Florida, Gainesville, FL, 32611, USA. Electronic address: cmartyn@ufl.edu.

Abstract

Acetochlor is a high-volume herbicide used on a global scale and toxicity assessments are needed to define its potential for adverse effects in wildlife and humans. This study was conducted to determine the effects of acetochlor on human liver carcinoma cells (HepG2), a cell model widely used to assess the potential for chemical hepatotoxicity. Experiments were conducted at concentrations ranging 0-800 μM acetochlor over a 12 to 48h period to quantify underlying mechanisms of toxicity. Our data indicate that acetochlor suppressed HepG2 cell proliferation in both a concentration- and time-dependent manner. Acetochlor induced reactive oxygen species (ROS) generation more than 700% with exposure to 400 μM acetochlor, and acetochlor decreased the activities and levels of anti-oxidant responses (superoxide dismutase, glutathione) following exposure to 100 μM, 200 μM and 400 μM acetochlor. Acetochlor also (1) induced HepG2 cell damage through apoptotic-signaling pathways; (2) enhanced intracellular free Ca2+ concentration (>400%); (3) decreased mitochondrial transmembrane potential (∼77%), and reduced ATP levels (∼65%) following exposure to 400 μM acetochlor compared to untreated cells. Notably, cell cycle progression was blocked at G0/G1 phase in HepG2 cells when treated for 24 h with 400 μM acetochlor. Taken together, acetochlor induced significant cytotoxicity toward HepG2 cells, and the underlying toxicity mechanisms appear to be related to ROS generation, mitochondrial dysfunction and disruption in the cell cycle regulation. These data contribute to toxicity assessments for acetochlor, a high-use herbicide, to quantify risk to wildlife and human health.

KEYWORDS:

Acetochlor; Cell apoptosis; Flow cytometry; HepG2 cells; Oxidative stress; Toxicity mechanisms

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center