PMID- 25176419 OWN - NLM STAT- MEDLINE DCOM- 20150804 LR - 20191210 IS - 1879-3177 (Electronic) IS - 0887-2333 (Linking) VI - 29 IP - 1 DP - 2015 Feb TI - Sterigmatocystin-induced oxidative DNA damage in human liver-derived cell line through lysosomal damage. PG - 1-7 LID - S0887-2333(14)00161-1 [pii] LID - 10.1016/j.tiv.2014.08.007 [doi] AB - Sterigmatocystin (STC) is a carcinogenic and mutagenic mycotoxin produced by fungi of many Aspergillus species. As a precursor of the aflatoxins, STC is a risk factor of liver cancer. The objective of this study is to investigate STC-induced DNA damage and underlying mechanisms. The single cell gel electrophoresis (SCGE) assay was applied to assess DNA damage induced by STC. To clarify the underlying mechanisms, we measured the intracellular generation of reactive oxygen species (ROS) using dichlorofluorescein diacetate as a fluorochrome. The level of oxidative DNA damage was evaluated by immunocytochemical analysis of 8-hydroxydeoxyguanosine (8-OHdG) and the acridine orange (AO) was used to measure the changes of lysosomal membrane stability. A significant dose-dependent increase of DNA strand breaks was found after treatment with STC (3 and 6 muM) respectively for 1 h. Increases in ROS level and the expression of 8-OHdG were also observed. A statistically significant increase in AO fluorescence intensity was observed in cells treated with STC (1.5, 3 and 6 muM) for 1 h. The DNA strand breaks induced by STC were almost prevented in cells pretreated with NH(4)Cl (10 mM) and NAC (10 mM) for 1 h. Our results thus indicated that STC exerts genotoxic effects on HepG2 cells, most likely through oxidative stress and lysosomal leakage. CI - Copyright (c) 2014 Elsevier Ltd. All rights reserved. FAU - Gao, Wei AU - Gao W AD - Department of Nutrition and Food Safety, Dalian Medical University, No. 9, West Segment of South lvshun Road, Dalian 116044, Liaoning, PR China; Natural Products Engineering Technology Center, Dalian Medical University, No. 9, West Segment of South lvshun Road, Dalian 116044, Liaoning, PR China. FAU - Jiang, Liping AU - Jiang L AD - China-Japanese Joint Institute for Medical and Pharmaceutical Science, Dalian Medical University, No. 9, West Segment of South lvshun Road, Dalian 116044, Liaoning, PR China; Natural Products Engineering Technology Center, Dalian Medical University, No. 9, West Segment of South lvshun Road, Dalian 116044, Liaoning, PR China. FAU - Ge, Lan AU - Ge L AD - Department of Pharmacy, Affiliated Hospital to Changchun University of Chinese Medicine, No. 1478 of Gongnong Road, Changchun 130021, Jilin, PR China. FAU - Chen, Min AU - Chen M AD - Department of Nutrition and Food Safety, Dalian Medical University, No. 9, West Segment of South lvshun Road, Dalian 116044, Liaoning, PR China. FAU - Geng, Chengyan AU - Geng C AD - China-Japanese Joint Institute for Medical and Pharmaceutical Science, Dalian Medical University, No. 9, West Segment of South lvshun Road, Dalian 116044, Liaoning, PR China; Natural Products Engineering Technology Center, Dalian Medical University, No. 9, West Segment of South lvshun Road, Dalian 116044, Liaoning, PR China. FAU - Yang, Guang AU - Yang G AD - Department of Nutrition and Food Safety, Dalian Medical University, No. 9, West Segment of South lvshun Road, Dalian 116044, Liaoning, PR China. FAU - Li, Qiujuan AU - Li Q AD - Department of Nutrition and Food Safety, Dalian Medical University, No. 9, West Segment of South lvshun Road, Dalian 116044, Liaoning, PR China. FAU - Ji, Fang AU - Ji F AD - Department of Nutrition and Food Safety, Dalian Medical University, No. 9, West Segment of South lvshun Road, Dalian 116044, Liaoning, PR China. FAU - Yan, Qiu AU - Yan Q AD - Department of Biochemistry & Molecular Biology, Dalian Medical University, No. 9, West Segment of South lvshun Road, Dalian 116044, Liaoning, PR China. FAU - Zou, Yang AU - Zou Y AD - Department of Radiotherapy, Affiliated Hospital 1 to Dalian Medical University, No. 222 of Zhongshan Road, Dalian 116011, Liaoning, PR China. FAU - Zhong, Laifu AU - Zhong L AD - China-Japanese Joint Institute for Medical and Pharmaceutical Science, Dalian Medical University, No. 9, West Segment of South lvshun Road, Dalian 116044, Liaoning, PR China; Natural Products Engineering Technology Center, Dalian Medical University, No. 9, West Segment of South lvshun Road, Dalian 116044, Liaoning, PR China. FAU - Liu, Xiaofang AU - Liu X AD - Department of Nutrition and Food Safety, Dalian Medical University, No. 9, West Segment of South lvshun Road, Dalian 116044, Liaoning, PR China. Electronic address: food@dlmedu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140828 PL - England TA - Toxicol In Vitro JT - Toxicology in vitro : an international journal published in association with BIBRA JID - 8712158 RN - 0 (Mycotoxins) RN - 10048-13-2 (Sterigmatocystin) RN - 88847-89-6 (8-Hydroxy-2'-Deoxyguanosine) RN - F30N4O6XVV (Acridine Orange) RN - G9481N71RO (Deoxyguanosine) SB - IM MH - 8-Hydroxy-2'-Deoxyguanosine MH - Acridine Orange MH - Comet Assay MH - DNA Damage/*drug effects MH - Deoxyguanosine/analogs & derivatives/metabolism MH - Dose-Response Relationship, Drug MH - Hep G2 Cells/drug effects MH - Humans MH - Lysosomes/*drug effects MH - Mycotoxins/*toxicity MH - Oxidation-Reduction/drug effects MH - Oxidative Stress/drug effects MH - Sterigmatocystin/*toxicity OTO - NOTNLM OT - DNA strand breaks OT - Lysosomal membrane permeabilization OT - Oxidative stress OT - Sterigmatocystin EDAT- 2014/09/02 06:00 MHDA- 2015/08/05 06:00 CRDT- 2014/09/02 06:00 PHST- 2014/03/08 00:00 [received] PHST- 2014/06/24 00:00 [revised] PHST- 2014/08/14 00:00 [accepted] PHST- 2014/09/02 06:00 [entrez] PHST- 2014/09/02 06:00 [pubmed] PHST- 2015/08/05 06:00 [medline] AID - S0887-2333(14)00161-1 [pii] AID - 10.1016/j.tiv.2014.08.007 [doi] PST - ppublish SO - Toxicol In Vitro. 2015 Feb;29(1):1-7. doi: 10.1016/j.tiv.2014.08.007. Epub 2014 Aug 28.