Involvement of reactive oxygen species in Microcystin-LR-induced cytogenotoxicity

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...

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Published inFree radical research Vol. 41; no. 12; pp. 1326 - 1337
Main Authors Nong, Qingqing, Komatsu, Masaharu, Izumo, Kimiko, Indo, Hiroko P., Xu, Baohui, Aoyama, Kohji, Majima, Hideyuki J., Horiuchi, Masahisa, Morimoto, Kanehisa, Takeuchi, Toru
Format Journal Article
LanguageEnglish
Published England Informa UK Ltd 01.12.2007
Taylor & Francis
Subjects
Bacterial Toxins - toxicity
Carcinoma, Hepatocellular
Cell Cycle - drug effects
Cell Line, Tumor
Comet Assay
CYP2E1
Cytochrome P-450 Enzyme System - genetics
cytogenotoxicity
Deoxyguanosine - analogs & derivatives
Deoxyguanosine - analysis
Humans
Immunohistochemistry
L-Lactate Dehydrogenase - analysis
Liver Neoplasms
Microcystin-LR
Microcystins - toxicity
oxidative damage
Polymerase Chain Reaction
reactive oxygen species (ROS)
Reactive Oxygen Species - metabolism
RNA, Messenger - genetics
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Summary: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.
ISSN:1071-5762
1029-2470
DOI:10.1080/10715760701704599