1. Effects of microcystins-LR on genotoxic responses in human intestinal epithelial cells (NCM460).
- Author
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Wen, Cong, Zheng, Shuilin, Yang, Yue, Li, Xiaoyu, Chen, Jihua, Wang, Xiaoyan, Feng, Xiangling, and Yang, Fei
- Subjects
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EPITHELIAL cells , *MICROCYSTINS , *DNA damage , *PHOSPHOPROTEIN phosphatases , *CYANOBACTERIAL toxins , *PROTEIN expression , *REACTIVE oxygen species , *P53 protein - Abstract
Microcystin-LR (MC-LR), a cyclic heptapeptide toxin produced by cyanobacteria, was found to induce genotoxic actions in various types of cells. Some investigators reported that microcystin-LR acted as tumor initiator in the observed genotoxic action mediated by this cyanotoxin. However, the underlying mechanisms underlying MC-induced DNA damage in the human intestine epithelium cell line (NCM460) are not known. The purpose of this study was to examine the influence of 24 hr exposure to 5 or 10 µM MC-LR on intestinal DNA damage using NCM460 intestine cell line as a model. Data showed that MC-LR increased Olive tail moment (OTM) as evidenced by the comet assay, inhibited protein phosphatase 2A (PP2A) activity, elevated reactive oxygen species levels (ROS) and enhanced γ-H2AX and p-p53 protein expression levels. Results indicated that MC-LR produced intestinal DNA damage by inhibiting PP2A activity, activating p53 protein and subsequently initiating excess generation of ROS. These observations suggest that MC-LR–induced intestinal DNA damage involves a complex series of events that include oxidant stress, PP2A enzymic inhibition and activation of p53 protein. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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