title: Alpha-tocopherol protects cultured human cells from the acute lethal cytotoxicity of dioxin.
abstract: The possible protection of cultured human cells from acute dioxin injury by antioxidants was investigated. The most potent dioxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), caused vacuolization of the smooth endoplasmic reticulum and Golgi apparatus in cultured human conjunctival epithelial cells and cervical cancer cells. Subsequent nuclear damage included a deep irregular indentation resulting in cell death. A dosage of 30-40 ng/mL TCDD induced maximal intracellular production of H2O2 at 30 minutes and led to severe cell death (0-31% survival) at two hours. A dose of 1.7 mM alpha-tocopherol or 1 mM L-dehydroascorbic acid significantly protected human cells against acute TCDD injuries (78-97% survivals), but vitamin C did not provide this protection. These results indicate that accidental exposure to fatal doses of TCDD causes cytoplasmic free radical production within the smooth endoplasmic reticular systems, resulting in severe cytotoxicity, and that vitamin E and dehydroascorbic acid can protect against TCDD-induced cell damage.
authors.affiliation: Department of Molecular Biology, California University, San Francisco, CA, USA. keih@kanazawa-med.ac.jp
authors.forename: Kei-Ichi
authors.initials: K
authors.lastname: Hirai
authors.forename: Jie-Hong
authors.initials: JH
authors.lastname: Pan
authors.forename: Ying-Bo
authors.initials: YB
authors.lastname: Shui
authors.forename: Eriko
authors.initials: E
authors.lastname: Simamura
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shimada
authors.forename: Toshito
authors.initials: T
authors.lastname: Kanamaru
authors.forename: Junko
authors.initials: J
authors.lastname: Koyama
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D003228:Conjunctiva; D003683:Dehydroascorbic Acid / Q000494:pharmacology; D004147:Dioxins / Q000494:pharmacology*; D018871:Endoplasmic Reticulum, Smooth / Q000648:ultrastructure; D004847:Epithelial Cells / Q000648:ultrastructure; D005260:Female; D006056:Golgi Apparatus / Q000648:ultrastructure; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008854:Microscopy, Electron; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D002583:Uterine Cervical Neoplasms / Q000648:ultrastructure; D014617:Vacuoles / Q000187:drug effects; D024502:alpha-Tocopherol / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D006861:Hydrogen Peroxide; D024502:alpha-Tocopherol; D001205:Ascorbic Acid; D003683:Dehydroascorbic Acid