title: 4-Methoxyestradiol-induced oxidative injuries in human lung epithelial cells.
abstract: Epidemiological studies indicated that people exposed to dioxins were prone to the development of lung diseases including lung cancer. Animal studies demonstrated that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increased liver tumors and promoted lung metaplasia in females. Metabolic changes in 17beta-estradiol (E(2)) resulted from an interaction between TCDD and E(2) could be associated with gender difference. Previously, we reported that methoxylestradiols (MeOE(2)), especially 4-MeOE(2), accumulated in human lung cells (BEAS-2B) co-treated with TCDD and E(2). In the present study, we demonstrate unique accumulation of 4-MeOE(2), as a result of TCDD/E(2) interaction and revealed its bioactivity in human lung epithelial cell line (H1355). 4-Methoxyestradiol treatment significantly decreased cell growth and increased mitotic index. Elevation of ROS and SOD activity, with a concomitant decrease in the intracellular GSH/GSSG ratio, was also detected in 4-MeOE(2)-treated cells. Quantitative comet assay showed increased oxidative DNA damage in the 4-MeOE(2)-treated H1355 cells, which could be significantly reduced by the anti-oxidant N-acetylcysteine (NAC). However, inhibition of cell growth and increase in mitotic arrest induced by 4-MeOE(2) were unaffected by NAC. We concluded that 4-MeOE(2) accumulation resulting from TCDD and E(2) interaction would contribute to the higher vulnerability on lung pathogenesis in females when exposed to TCDD.
authors.affiliation: Department of Physiology, Collage of Medicine, China Medical University, 91 Shueh-Shih Road 40402, Taiwan, ROC.
authors.forename: Yahsin
authors.initials: Y
authors.lastname: Cheng
authors.forename: Louis W
authors.initials: LW
authors.lastname: Chang
authors.forename: Li-Chuan
authors.initials: LC
authors.lastname: Cheng
authors.forename: Ming-Hsien
authors.initials: MH
authors.lastname: Tsai
authors.forename: Pinpin
authors.initials: P
authors.lastname: Lin
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004958:Estradiol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D019803:Glutathione Disulfide / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008940:Mitotic Index; D008954:Models, Biological; D018384:Oxidative Stress / Q000187:drug effects*; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D008941:Spindle Apparatus / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D014404:Tubulin / Q000187:drug effects
chemical_list: D016166:Free Radical Scavengers; D000072317:Polychlorinated Dibenzodioxins; D017382:Reactive Oxygen Species; D014404:Tubulin; C045018:4-methoxyestradiol; D004958:Estradiol; D013482:Superoxide Dismutase; D019803:Glutathione Disulfide; D000111:Acetylcysteine