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.
Subject(s)
Chlorophenols/toxicity , Gene Expression/drug effects , Liver Neoplasms, Experimental/metabolism , Oxidative Stress/drug effects , Actins/genetics , Animals , Antioxidants/metabolism , Aryl Hydrocarbon Hydroxylases/genetics , Carcinoma, Hepatocellular , Cell Survival/drug effects , Cytochrome P-450 CYP2E1/genetics , Cytochrome P-450 CYP3A , Cytochrome P-450 Enzyme System/genetics , Cytochrome P-450 Enzyme System/metabolism , Glutathione/metabolism , Humans , In Vitro Techniques , Liver Neoplasms, Experimental/enzymology , Malondialdehyde/metabolism , Proteins/metabolism , RNA, Neoplasm/genetics , RNA, Neoplasm/metabolism , Toxicity Tests , Tumor Cells, CulturedABSTRACT
Intoxication by pure polychlorobiphenyls and a commercial product is studied, in rats, after intraperitoneal and oral administration. Their fixation and excretion of their metabolites is greater by intraperitoneal than by oral administration. The only hydroxy metabolites, identified by means of synthesis, gas chromatography and mass spectrometry are, all, derivatives from trichlorobiphenyl. It appears that administration of commercial product induces a more rapid degradation of these compounds in animal organism.
