Dimethylacetamide-induced Hepatic Injury in Vitro: Mechanism and Potential Preventive Strategy / 生物医学与环境科学（英文）

N,N-Dimethylacetamide (DMAc) is a widely used organic solvent in modern chemical industry with low to moderate hepatotoxicity to occupational health of employees. But so far, there are fewer and less conclusive data concerning its pathogenic mechanism in detail. In current study, the toxicity of DMAc was firstly investigated on human normal hepatocytes (LO-2), using a series of molecular biology measurements to ananlyze the effect and mechanism of DMAc-induced hepatic cell injury and explore effective prophylactic measures. We found that DMAc triggered LO-2 apoptosis in a obviously dose-dependent manner, caused by increased ROS generation and activation of Bcl-2 pathway. Significantly, glutathione (GSH) rather than vitamin C (Vit C) could partially inhibit DMAc-induced apoptosis thus showing potential as a effective precaution for workers.

JWA regulates N-methyl-N'-nitro-N-nitrosoguanidine induced malignant transformation in human bronchial epithelial cells / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the role and possible mechanism of JWA in N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) inducing human bronchial epithelial (HBE) cells' neoplastic transformation.</p><p><b>METHODS</b>JWA overexpression vector and its stable transfection HBE cells were established. The characteristics of transformed HBE cells were determined by methyl thiazolyl tetrazolium (MTT) assay and the soft agar colony formation assay. The expressions of JWA and P53 were detected by Western blot.</p><p><b>RESULTS</b>The growth rates of the HBE cells which were treated with MNNG were significantly accelerated than the JWA overexpression HBE cells and controlled HBE cells (P < 0.05). The soft agar colony formation of JWA overexpression HBE cells with and without MNNG treatment (8.06% and 10.14%) was significantly lower than that of the normal HBE cells with MNNG treatment (26.80%) (P < 0.01). After exposure of MNNG, the P53 expressions were gradually increased in HBE cells with the increased passages. However, the expression of P53 in JWA over expressed HBE cells showed a different manner. P53 reached an over expression peak at early stage (the first passage), and then with a gradually down-regulated expression spectrum with increased passages of the cells.</p><p><b>CONCLUSION</b>JWA might be a key molecule and play an important role in MNNG inducing neoplastic transformation in HBE cells through regulation of the expression of P53.</p>

The role of JWA in N-methyl-N'-nitro-N-nitrosoguanidine induced human bronchial epithelial cell apoptosis / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the role and possible mechanism of JWA in N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induced human bronchial epithelial (HBE) cell apoptosis.</p><p><b>METHODS</b>The cell growth inhibition rate was detected by MTT, the cell apoptosis was measured by Hoechst staining, the expression of JWA protein was detected by Western blot, and the potential binding protein of JWA proximal promoter was detected by Southwestern assay.</p><p><b>RESULTS</b>MNNG treatment of HBE cells for 24 hours induced apoptosis with significant dose-effect relationship and in this course the expression of JWA protein was elevated. The 2.0 microg/ml MNNG treated cells for 24 hours activated nuclear transcription factor expression that specifically bound to JWA proximal promoter.</p><p><b>CONCLUSION</b>That MNNG treatment activates nuclear transcription factor binding to JWA proximal promoter may be involved in intracellular apoptosis associated signal pathway.</p>