| Chlorophenols are a class of aromatic hydrocarbons, whose hydrogen atoms(one to five) were replaced by chlorine atoms on the benzene ring. According to the number substituted chlorine atoms, chlorophenols are classified five categories: monochlorophenol, dichlorophenol(DCP), trichlorophenol(TCP), tetrachlorophenol(Te CP), pentachlorophenol(PCP). Chlorophenols are soluble in organic solvents, such as dimethyl sulfoxide, benzene and so on, but only slightly soluble or insoluble in water. What’s more, the solubility in water decreased with the increased chlorine atoms. Chlorophenols are widely used in agriculture and industry as pesticides, herbicides and preservatives, which could enter environment and accumulate in the food chain. So far, many countries have listed a variety of chlorophenols as priority pollutants. Because of the stable chemical structure, chlorophenols are difficult to be degraded in natural environment, and belong to persistent organic environmental pollutants. 2,4,6-trichlorophenol is a toxic one among chlorophenols, which was defined by World Health Organization as a carcinogen. For the broad distribution and difficult degradation as well as high toxicity, the toxicity studies on 2,4,6-trichlorophenol have important practical significance. This study explored the impacts of 2,4,6-trichlorophenol treatment on mouse fibroblast cells for better toxicity prevention.The results of this study are shown as follows:1. After 12 h of 2,4,6-trichlorophenol treatment, the cell viability of mouse fibroblasts were reduced and cell morphology were altered. At a concentration of 0.25, 0.5, 0.75, and 1.0 m M, cell viability decreased with the increased concentration of 2,4,6-TCP. Cell morphology was altered significantly by 1.0 m M 2,4,6-TCP treatment.2. 2,4,6-TCP treatment caused oxidative stress in mouse fibroblasts. ROS reached a breaking point after one hour of the treatment. At 1 h to 2 h after treatment, ROS decreased gradually. However, ROS reached second outbreak levels at 2 h to 4 h after exposed to 2,4,6-TCP, after which ROS reduced. In this study, two indictors were selected to detect ROS level s: Nrf2 and HO-1. 2,4,6-trichlorophenol induced the expression of Nrf2 and HO-1. The m RNA levels of Nrf2 and HO-1 were increased with the increased concentration of 2,4,6-trichlorophenol. Nrf2 protein focus were also increased after 2,4,6-trichlorophenol exposure.3. 2,4,6-trichlorophenol treatment induced endoplasmic reticulum stress pathway in mouse fibroblasts. After 12 h treatment, the expression of IRE1α, Bip and splice type XBP1 increased significantly. The transformation rate of full-length XBP1 to splice type XBP1 increased with the increased concentration of 2,4,6-trichlorophenol. The levels of Bip and CHOP, the maker proteion of endoplasmic reticulum stress, also increased with the concentration of 2,4,6-trichlorophenol, which further confirmed that 2,4,6-trichlorophenol induced endoplasmic reticulum stress. EIF2α phosphorylation got a maximum at concentrations of 0.5 and 0.75 m M.4. 2,4,6-trichlorophenol treatment induced apoptosis of mouse fibroblasts. Using flow cytometry method, the apoptosis of mouse fibroblasts were analysised after 2,4,6-trichlorophenol treatment. The rate of apoptosis was increased with the increasing exposure concentration. The activities of caspase also increased with the exposure time, and reached the highest level at 12 h after treatment. The mitochondrial membrane potential, which could reflect the apoptosis, decreased to a lowest level at 1.0 m M treatment.The ratio of Bax/Bcl-2 resprent the level of apoptosis.Conclusion: The cell exposed to 2,4,6-TCP decreased the MEF cell vitality, at the same time induced oxidative stress, endoplasmic reticulum stress and apoptosis. |
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