Effects of microcystins-LR on genotoxic responses in human intestinal epithelial cells (NCM460)

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.

KEYWORDS:

• MC-LR
• genotoxicity
• intestine
• PP2A
• ROS

Acknowledgments

The authors are very grateful to Professor Sam Kacew from Canada for revising and editing paper.

Additional information

Funding

This research was supported by the National Natural Science Foundation of China [81773393, 81502787], Central South University Innovation Driven Project [20170027010004], Key Research and Development Projects in Hunan Province [2019SK2041, 2018WK2013] and the National Key Research and Development Program of China [2016YFC0900800], the Ministry of Science and Technology of China [2015FY111100, 2016YFC0900802], the graduate students independent exploration and innovation project of Central South University [2018zzts856].