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.
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Authors | Yahsin Cheng, Louis W Chang, Li-Chuan Cheng, Ming-Hsien Tsai, Pinpin Lin |
Journal | Toxicology and applied pharmacology
(Toxicol Appl Pharmacol)
Vol. 220
Issue 3
Pg. 271-7
(May 01 2007)
ISSN: 0041-008X [Print] United States |
PMID | 17397890
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Free Radical Scavengers
- Polychlorinated Dibenzodioxins
- Reactive Oxygen Species
- Tubulin
- 4-methoxyestradiol
- Estradiol
- Superoxide Dismutase
- Glutathione Disulfide
- Acetylcysteine
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Topics |
- Acetylcysteine
(pharmacology)
- Cell Line
- Cell Proliferation
(drug effects)
- Comet Assay
- DNA Damage
- Dose-Response Relationship, Drug
- Epithelial Cells
(drug effects, metabolism, pathology)
- Estradiol
(analogs & derivatives, metabolism, pharmacology)
- Female
- Free Radical Scavengers
(pharmacology)
- Glutathione Disulfide
(metabolism)
- Humans
- Lung
(drug effects, metabolism, pathology)
- Mitotic Index
- Models, Biological
- Oxidative Stress
(drug effects)
- Polychlorinated Dibenzodioxins
(pharmacology)
- Reactive Oxygen Species
(metabolism)
- Spindle Apparatus
(drug effects)
- Superoxide Dismutase
(metabolism)
- Tubulin
(drug effects)
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