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

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.

• Authors: Tao Huang, Ying Huang, Yu Huang, Yi Yang, Yuanhui Zhao, Christopher J Martyniuk
• Journal: Chemosphere (Chemosphere) Vol. 243 Pg. 125345 (Mar 2020) ISSN: 1879-1298 [Electronic] England
• PMID: 31739254 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.

Chemical References

• Herbicides
• Reactive Oxygen Species
• Toluidines
• acetochlor
• Glutathione

Topics

• Apoptosis (drug effects)
• Carcinoma, Hepatocellular (pathology)
• Cell Cycle Checkpoints (drug effects)
• Cell Line
• Glutathione (metabolism)
• Hep G2 Cells
• Herbicides (toxicity)
• Humans
• Liver Neoplasms (pathology)
• Membrane Potential, Mitochondrial (drug effects)
• Reactive Oxygen Species (metabolism)
• Toluidines (toxicity)
• Toxicity Tests