Activation of 4-aminobiphenyl mediated by 5-lipoxygenase and DNA damage in human bronchial epithelial cells

The effect of 4-aminobiphenyl (4-ABP) on 5-lipoxygenase (5-LOX) protein expression, cytotoxicity, and DNA damage in human bronchial epithelial (HBE) cells was studied to provide evidence that LOX is a pathway for oxidation and activation of pre-carcinogens. Enzymic experiment: soybean lipoxygenase (SLO), substrate (4-ABP) and other components reacted in an enzymic system; the product was detected with spectrophotometry. Cellular experiment: the effect of 4-ABP on the cellular survival rate was assessed by reduction of tetrazolium dye (MTT) in cultured HBE cells. After HBE cells were exposed to 4-ABP 100-800 M for 4 h, the protein expression of 5-LOX in HEB cells was tested by Western blotting, and DNA damage by single cell gel electrophoresis. Finally the effect of specific inhibitors of 5-LOX, AA861, on 5-LOX protein expression and DNA damage in the cells was detected. The authors found that SLO catalysed the co-oxidation of 4-ABP in the presence of H2O2. Nordihydroguaiaretic acid (NDGA) inhibited the oxidation of 4-ABP by SLO, seemingly in a concentration dependent manner and with in a special range. 4-ABP induced 5-LOX protein expression, but AA861 was invalid in HBE. 4-ABP caused toxic action and DNA damage in HBE, as the pos. rate comet cells was increased to 47.7% by 4-ABP at 400 M. Such damage could be significantly inhibited by AA861 and naproxen with a maximum rate of protection of 58.1% and 21.7%, respectively. 4-ABP can regulate 5-LOX protein expression in HBE cells. The co-oxidation of 4-ABP with 5-LOX could induce DNA damage, which could be one of the mechanisms for carcinogenesis of 4-ABP.

Authors: Zhu, Hongxiang; Hu, Jianan; Huang, Yun; Wu, Yue; Xiong, Minru ;Full Source: Zhongguo Yaolixue Yu Dulixue Zazhin 2011, 25(2), 193-200 (Ch) ;