Involvement of oxidative sress in the toxicity of 4‐monochlorophenol in Hep G2 cells in culture

Abstract

Chlorophenols, mainly used as biocides, are compounds with a wide spectrum of toxic effects, including teratogenic and carcinogenic actions. The aim of this study was to examine possible 4-monochlorophenol (4-MCP) toxicity related to metabolic pathways, which may implicate semiquinones and reactive oxygen species (ROS), in human Hep G2 cells. The effects of 4-MCP were performed through cytotoxicity assays (viability, ATP level), metabolic activities (4-MCP intracellular concentration, NADPH cytochrome P-450 reductase (Cyt P-450 red.) and glutathione-S-transferase activities, CYP 3A7 mRNA expression) and oxidative stress (superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities, glutathione status, malondialdehyde concentration, CYP 2E1 mRNA expression). According to the literature, in this work Hep G2 cells were incubated in the continuous presence of 4-MCP at 350 microM over 24 or 48 h. Results showed statistically significant decreases in ATP levels (24 or 48 h, P < 0.05) versus controls. The 4-MCP intracellular concentrations increased as early as 8-24 h and then decreased (P < 0.01). Decreases in Cyt. P-450 red. (24 h, P < 0.05), catalase (24 h, P < 0.05; 48 h, P < 0.01), glutathione peroxidase activities (48 h, P < 0.05) and reduced glutathione concentrations (48 h, P < 0.05) were observed. In addition, exposure to 4-MCP increased mRNA expressions of CYP 3A7 (24 h, P < 0.05; 48 h, P < 0.01) and CYP 2E1 (24 h, P < 0.01) versus controls. Taken together, these results suggest that 4-MCP metabolites could induce oxidative stress conditions in Hep G2 cells.

Glutathione S‐transferase theta genotypes and environmental exposures in the risk of canine transitional cell carcinoma

“…2,4‐Dichlorophenoxyacetic acid (2,4‐D) is the most common phenoxyherbicide in household use, and has been found in canine urine after lawn exposures . Although 2,4‐D does not appear to be directly mutagenic, its soil metabolites are reactive and mutagenic . Follow‐up studies are needed to measure concentrations of specific herbicides and insecticides in the urine of dogs with TCC, compared to controls.…”

“…4 Although 2,4-D does not appear to be directly mutagenic, its soil metabolites are reactive and mutagenic. 52,53 Follow-up studies are needed to measure concentrations of specific herbicides and insecticides in the urine of dogs with TCC, compared to controls.…”