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Int J Toxicol. 2019 Mar/Apr;38(2):121-128. doi: 10.1177/1091581819827495. Epub 2019 Feb 10.

Lipoxygenase Protein Expression and Its Effect on Oxidative Stress Caused by Benzidine in Normal Human Urothelial Cell Lines.

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1 Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha, China.
2 Changsha Center for Disease Control and Prevention, Changsha, China.
3 Changde Center for Disease Control and Prevention, Changde, China.
4 Hunan Provincial Center for Disease Control and Prevention, Changsha, China.
5 Shanxi Provincial Center for Disease Control and Prevention, Taiyuan, China.


Metabolic activation of indirect-acting carcinogens in the target organ is an effective mechanism of carcinogenesis. Lipoxygenase (LOX) can co-oxidize the bladder carcinogen benzidine (BZ). However, it is not entirely clear whether BZ is activated and which enzyme is involved in its activation in bladder epithelial cells. Our results showed that BZ induced 5-LOX protein expression but had no significant influence on the expression of 15-LOX-2, CYP1B1, and CYP2E1 in SV-40 immortalized human uroepithelial SV-HUC-1 cells. BZ induced oxidative stress in SV-HUC-1 cells by increasing reactive oxygen species (ROS) and malondialdehyde levels significantly in the 100 and 200 μmol/L-BZ-treated groups and decreased the level of the antioxidant reduced glutathione significantly at 200 μmol/L BZ. Concurrently, the activity of catalase was increased, while the activity of superoxide dismutase was increased at 50 μmol/L BZ but gradually decreased with increasing concentrations of BZ ( P < 0.05). However, the oxidative stress and damage in SV-HUC-1 cells caused by BZ were effectively inhibited by the 5-LOX-specific inhibitor AA861 at 10 μmol/L. Thus, 5-LOX is probably the major LOX isozyme to co-oxidize exogenous chemicals in SV-HUC-1 cells. AA861 has a protective effect on the oxidative stress and damage induced by BZ in SV-HUC-1 cells. We conclude that BZ can be activated by 5-LOX to produce ROS and oxidative stress, which may be associated with bladder cancer caused by BZ.


AA861; benzidine; lipoxygenase; oxidative stress


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