title: Oxidative DNA damage induced by di-(2-ethylhexyl) phthalate in HEK-293 cell line.
abstract: Di-(2-ethylhexyl) phthalate (DEHP) is commonly employed as a plasticizer. We have found that exposure of human embryonic kidney cell line 293 (HEK-293) to DEHP resulted in a crucial dose-dependent increase of DNA strand breaks in a comet assay. To elucidate the role of glutathione (GSH) in the DNA damage, the cells were pretreated with buthionine-(S,R)-sulfoximine (BSO) and pretreated with N-acetylcysteine (NAC), a GSH precursor. Here we show that depletion of GSH in HEK-293 cells with BSO dramatically increased the susceptibility of HEK-293 cells to DEHP-induced DNA damage. Furthermore, when the intracellular GSH content was elevated by NAC, the DNA damage induced by DEHP was almost completely abolished. In addition, DEHP had effect on lysosomal or mitochondrial damage at high dose level. These results indicate that DEHP exerts genotoxic effects in HEK-293 cells, probably through DNA damage induced by oxidative stress; GSH is responsible for cellular defense against DEHP-induced DNA damage; lysosome and mitochondria may be the vital targets in DEHP-induced DNA damage.
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: Xuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, The Affiliated Zhong Shan Hospital of Dalian University, Dalian, 116001 Liaoning, PR China.
authors.forename: Lijie
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: 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: Fang
authors.initials: F
authors.lastname: Ji
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: Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI 02903, USA.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Guan
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: D000111:Acetylcysteine / Q000494:pharmacology; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008247:Lysosomes / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D018384:Oxidative Stress; D010968:Plasticizers / Q000633:toxicity*
chemical_list: D010968:Plasticizers; D019328:Buthionine Sulfoximine; D004051:Diethylhexyl Phthalate; D005978:Glutathione; D000111:Acetylcysteine
keywords: DNA strand breaks; Di-(2-ethylhexyl) phthalate; Glutathione; HEK-293 cells; Lysosomal membrane stability; Mitochondrial membrane potential