Cellular effects of metolachlor exposure on human liver (HepG2) cells

• Published in: Chemosphere (Oxford) 2013-01, Vol.90 (3), p.1258-1266
• Main Authors: Hartnett, Sean, Musah, Sadiatu, Dhanwada, Kavita R.
• Format: Article
• Language: English
• Subjects: Acetamides - toxicity; Biological and medical sciences; Cell cycle; Cell Cycle - drug effects; Cell Proliferation - drug effects; Cyclin A - genetics; Cyclins; Cytotoxins - toxicity; Hep G2 Cells - cytology; Hep G2 Cells - drug effects; Hep G2 Cells - metabolism; HepG2 liver cell growth; Herbicides - toxicity; Humans; Medical sciences; Metolachlor; Pesticides, fertilizers and other agrochemicals toxicology; Toxicology; Transcription, Genetic - drug effects
• ISSN: 0045-6535; 1879-1298
• DOI: 10.1016/j.chemosphere.2012.09.077

► HepG2 cells – immortalized human liver cell line. ► 50 parts per billion metolachlor inhibits growth of HepG2 cells. ► Metolachlor exposure results in reduced cell division rate. ► HepG2 cell cycle progression altered after metolachlor exposure. ► Decrease of cyclin A transcripts after metolachlor exposure in HepG2 cells. Metolachlor is one of the most commonly used herbicides in the United States. Protein synthesis is inhibited when roots and shoots of susceptible plants absorb this synthetic herbicide. While quite effective in killing weeds, several studies have shown that exposure to metolachlor results in decreased cell proliferation, growth and reproductive ability of non-target organisms. However, the mode of metolachlor action in non-target organisms has not yet been elucidated. The current study assessed effects of metolachlor exposure on immortalized human liver (HepG2) cells. Results from cell proliferation assays showed that a 72-h exposure to 50parts per billion (ppb) metolachlor significantly inhibited growth of these cells compared to untreated controls while a decrease in the cell division rate required exposure to 500ppb metolachlor for 48h. Flow cytometry analysis of cell cycle distribution revealed that 500ppb metolachlor treatment resulted in fewer HepG2 cells in G2/M phase after 72h. Real-time PCR analysis showed a significant decrease in the abundance of the cyclin A transcripts after 12h in cells exposed to 300ppb metolachlor. These results suggest metolachlor may affect progression through the S phase of the cell cycle and entrance into the G2 phase.