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The formulation of most pesticides is proprietary and individual components are therefore not generally known.In a preliminary study,we identified six compounds that are often present in pesticides,of which 4-nonylphenyl-polyethylene glycol (NP-40) was found to be the most toxic.In this study,we investigated the toxicity of NP-40 and underlying mechanism in neuronal SK-N-SH cells.Exposure to NP 40 at concentrations higher than 60 μmol/L for 24 hr decreased cell viability.The cytotoxicity of NP-40 was time-and concentration-dependent Nuclear fragmentation and chromatin condensation were apparent starting at 50 μmol/L NP-40,and increased at higher concentrations.The expression of apoptotic factors including p53 and B-cell lymphoma (Bcl)-2-associated X protein was upregulated,while that of the anti-apoptotic marker Bcl-2 was downregulated at 80 μmol/L NP-40.Cytochrome c release was observed from 80 to 100 μmol/L by confocal microscopy.Caspase-9 and-3/7 activities increased according to concentration,and fluorescence-activated cell sorting analysis showed that apoptosis was induced at 50 μmol/L and was increased at 80 μmol/L.Our findings indicate that NP-40 stimulates the mitochondrial-mediated apoptosis pathway and reactive oxygen species production in a concentration-dependent manner,and suggest that antioxidant administration may be an effective treatment for patients with acute NP-40 poisoning.