期刊
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES
卷 82, 期 21, 页码 1113-1119出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15287394.2019.1698498
关键词
MC-LR; genotoxicity; intestine; PP2A; ROS
资金
- 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]
- National Key Research and Development Program of China [2016YFC0900800]
- Ministry of Science and Technology of China [2015FY111100, 2016YFC0900802]
- graduate students independent exploration and innovation project of Central South University [2018zzts856]
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 mu M 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 gamma-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.
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