ROS-triggered signaling pathways involved in the cytotoxicity and tumor promotion effects of pentachlorophenol and tetrachlorohydroquinone

Hsiu Min Chen, Yu-Hsuan Lee, Ying-Jan Wang

研究成果: Review article

10 引文 斯高帕斯(Scopus)


Free radical-triggered tissue damage is believed to play an essential role in a variety of human diseases. Pentachlorophenol (PCP) is applied as a pesticide worldwide in both industries and homes. It is used extensively as a biocide and wood preservative. Tetrachlorohydroquinone (TCHQ) was proved as a major toxic metabolite of PCP, contributing the release of free radicals during PCP metabolism. PCP has been proposed as a tumor promoter; however, only limited knowledge is available regarding the mechanisms of tumor promotion induced by PCP and its metabolite, TCHQ. A growing amount of literature suggests that a link between reactive oxygen species (ROS) and tumor promotion could exist. Herein, we summarize the findings regarding the ROS-triggered signaling pathways involved in the cytotoxicity and tumor promotion effects of PCP and TCHQ. Some of the notable findings demonstrated that TCHQ can induce DNA lesions and glutathione depletion in mammalian cells; meanwhile, oxidative stress and apoptosis/necrosis can be found both in vivo and in vitro. Interestingly, PCP and TCHQ were proved as mild tumor promoters in two-stage tumorigenesis models, in which the possible mechanism could be through ROS generation and changed Bcl-2 gene expression. We also found significant effects of antioxidants in attenuating the oxidative stress, cyto- and genotoxicity, and apoptosis/necrosis induced by PCP and/or TCHQ. In addition, mitogen-activated protein kinase (MAPK) activation is involved in PCP/TCHQ-triggered cytotoxicity, as evidenced by the finding that higher doses of TCHQ could lead to necrosis of freshly isolated splenocytes through the production of a large amount of ROS and sustained ERK activation. These results could explain partly the underlying molecular mechanisms contributing to the tumorigenesis induced by PCP. However, the detailed mechanisms of free radicals in triggering PCP/TCHQ-mediated tumor promotion and toxicity are still not completely resolved and need to be investigated further.

頁(從 - 到)339-350
期刊Chemical Research in Toxicology
出版狀態Published - 2015 三月 16


All Science Journal Classification (ASJC) codes

  • Toxicology