title: Response of antioxidant defense system to chromium (VI)-induced cytotoxicity in human diploid cells.
abstract: The aim of this study is to establish antioxidant indicators of chromium toxicity in fetal human lung fibroblasts (HLF). The results obtained corroborate and develop our earlier observation of low-dose and long-term action of Cr(VI) on human cells in culture. In the case of a nontoxic chromium dose, temporary oxidative stress is overcome by increased activity of the antioxidant system with correlation to cell cycle re-entry. The toxic concentrations misbalance the cell antioxidant defense systems and cause irreversible growth arrest and massive cell death by apoptosis. Sub-toxicity is defined as toxicity stretched in time. The activity of GPx (glutathione peroxidase) is proposed as a biomarker of oxidative stress caused by Cr(VI), and the GR (glutathione reductase) inhibition is considered as a marker of the toxicity developed under the complex Cr(VI) action. In HLF cells the glutathione dependent defense system is the first system destroyed in response to toxic chromium action. Only the balance between SOD (superoxide dismutase) and H(2)O(2) degrading enzymes (catalase and GPx), should play an important role in the fate of a cell, not individual enzymes.
authors.affiliation: Andronikashvili Institute of Physics, 0177 Tbilisi, Georgia.
authors.forename: Nino
authors.initials: N
authors.lastname: Asatiani
authors.forename: Marina
authors.initials: M
authors.lastname: Abuladze
authors.forename: Tamar
authors.initials: T
authors.lastname: Kartvelishvili
authors.forename: Nina
authors.initials: N
authors.lastname: Kulikova
authors.forename: Lali
authors.initials: L
authors.lastname: Asanishvili
authors.forename: Hoi-Ying
authors.initials: HY
authors.lastname: Holman
authors.forename: Nelly
authors.initials: N
authors.lastname: Sapojnikova
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002857:Chromium / Q000633:toxicity*; D004171:Diploidy; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D002857:Chromium; C074702:chromium hexavalent ion; D002374:Catalase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase