4-Methoxyestradiol-induced oxidative injuries in human lung epithelial cells.
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.
Cheng
Yahsin
Y
Department of Physiology, Collage of Medicine, China Medical University, 91 Shueh-Shih Road 40402, Taiwan, ROC.
Chang
Louis W
LW
Cheng
Li-Chuan
LC
Tsai
Ming-Hsien
MH
Lin
Pinpin
P
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
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