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Updated: Apr 27, 2026

Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling
Published on: March 20, 2018
RNA Interference Protects Against 5-Lipoxygenase-Induced Cocarcinogen, Benzidine, Oxidation and Cytotoxicity in Human
Yun Huang1, Qingping Tan2, Yue Wu1
1Department of Occupational and Environmental Health, School of Public Health, Central South University, Changsha, China.
Abstract:
Lipoxygenase (LOX)-catalyzed cooxidation of the human carcinogen benzidine (BZD) has been shown in in vitro enzyme systems. 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.
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