RNA Interference Protects Against 5-Lipoxygenase-Induced Cocarcinogen, Benzidine, Oxidation and Cytotoxicity in Human Tracheobronchial Epithelial Cells

This study aimed to determine whether BZD could be activated by arachidonate 5-lipoxygenase (ALOX5) in the human tracheobronchial epithelial cells (HBECs) using RNA interference strategy and a 5-LOX-specific inhibitor, AA861. We show that the soybean LOX catalyzed the cooxidation of BZD, generating BZD diimine. Benzidine induced expression of ALOX5 messenger RNA and 5-LOX protein in HBECs, and significantly decreased cell proliferation, but enhanced DNA damage and apoptosis in HBECs which were significantly inhibited by lentiviral-mediated small hairpin RNA-knockdown of ALOX5 and by AA861. Thus, BZD could upregulate the expression of ALOX5 in HBECs, while inhibition of the protein or gene expression or enzyme activity could prevent BZD-induced cytotoxicity and DNA damage in HBECs, which might be caused by the 5-LOX-catalyzed oxidative activation of BZD.

Source: International Journal of Toxicology - August 5, 2014 Category: Toxicology Authors: Huang, Y., Tan, Q., Wu, Y., Zhu, H., Xiong, M., Hu, J. Tags: Regular Articles Source Type: research