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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.<\/jats:p>","DOI":"10.1177\/1091581814542030","type":"journal-article","created":{"date-parts":[[2014,7,8]],"date-time":"2014-07-08T00:52:16Z","timestamp":1404780736000},"page":"297-306","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["RNA Interference Protects Against 5-Lipoxygenase-Induced Cocarcinogen, Benzidine, Oxidation and Cytotoxicity in Human Tracheobronchial Epithelial Cells"],"prefix":"10.1177","volume":"33","author":[{"given":"Yun","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Occupational and Environmental Health, School of Public Health, Central South University, Changsha, 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