Involvement of reactive oxygen species in Microcystin-LR-induced cytogenotoxicity |
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| Authors: | Nong Qingqing Komatsu Masaharu Izumo Kimiko Indo Hiroko P Xu Baohui Aoyama Kohji Majima Hideyuki J Horiuchi Masahisa Morimoto Kanehisa Takeuchi Toru |
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| Affiliation: | a Department of Environmental Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, Japanb Department of Oncology and Department of Space Environmental Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, Japanc Department of Social and Environmental Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, Japan |
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| Abstract: | ![]()
Microcystin-LR (MCLR) is a potent hepatotoxin. Oxidative stress is thought to be implicated in the cytotoxicity of MCLR, but the mechanisms by which MCLR produces reactive oxygen species (ROS) are still unclear. This study investigated the role and possible sources of ROS generation in MCLR-induced cytogenotoxicity in HepG2, a human hepatoma cell line. MCLR increased DNA strand breaks, 8-hydroxydeoxiguanosine formation, lipid peroxidation, as well as LDH release, all of which were inhibited by ROS scavengers. ROS scavengers partly suppressed MCLR-induced cytotoxicity determined by the MTT assay. MCLR induced the generation of ROS, as confirmed by confocal microscopy with 2-[6-(4'-hydroxy)phenoxy-3H-xanthen-3-on-9-yl]benzoic acid, and upregulated the expression of CYP2E1 mRNA. In addition, CYP2E1 inhibitors chlormethiazole and diallyl sulphide inhibited both ROS generation and cytotoxicity induced by MCLR. The results suggest that ROS contribute to MCLR-induced cytogenotoxicity. CYP2E1 might be a potential source responsible for ROS generation by MCLR. |
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| Keywords: | Microcystin-LR cytogenotoxicity reactive oxygen species (ROS) oxidative damage CYP2E1 |
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