title: Sterigmatocystin-induced oxidative DNA damage in human liver-derived cell line through lysosomal damage.
abstract: 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 μM) 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 μM) 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.
authors.affiliation: 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.
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.affiliation: 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.
authors.forename: Liping
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Pharmacy, Affiliated Hospital to Changchun University of Chinese Medicine, No. 1478 of Gongnong Road, Changchun 130021, Jilin, PR China.
authors.forename: Lan
authors.initials: L
authors.lastname: Ge
authors.affiliation: Department of Nutrition and Food Safety, Dalian Medical University, No. 9, West Segment of South lvshun Road, Dalian 116044, Liaoning, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Chengyan
authors.initials: C
authors.lastname: Geng
authors.affiliation: Department of Nutrition and Food Safety, Dalian Medical University, No. 9, West Segment of South lvshun Road, Dalian 116044, Liaoning, PR China.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Nutrition and Food Safety, Dalian Medical University, No. 9, West Segment of South lvshun Road, Dalian 116044, Liaoning, PR China.
authors.forename: Qiujuan
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Nutrition and Food Safety, Dalian Medical University, No. 9, West Segment of South lvshun Road, Dalian 116044, Liaoning, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Ji
authors.affiliation: Department of Biochemistry & Molecular Biology, Dalian Medical University, No. 9, West Segment of South lvshun Road, Dalian 116044, Liaoning, PR China.
authors.forename: Qiu
authors.initials: Q
authors.lastname: Yan
authors.affiliation: Department of Radiotherapy, Affiliated Hospital 1 to Dalian Medical University, No. 222 of Zhongshan Road, Dalian 116011, Liaoning, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zou
authors.affiliation: 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.
authors.forename: Laifu
authors.initials: L
authors.lastname: Zhong
authors.affiliation: 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.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Liu
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000165:Acridine Orange; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells / Q000187:drug effects; D006801:Humans; D008247:Lysosomes / Q000187:drug effects*; D009183:Mycotoxins / Q000633:toxicity*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D013241:Sterigmatocystin / Q000633:toxicity*
chemical_list: D009183:Mycotoxins; D013241:Sterigmatocystin; D000080242:8-Hydroxy-2'-Deoxyguanosine; D000165:Acridine Orange; D003849:Deoxyguanosine
keywords: DNA strand breaks; Lysosomal membrane permeabilization; Oxidative stress; Sterigmatocystin