Response of antioxidant defense system to chromium (VI)-induced cytotoxicity in human diploid cells.
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.
Asatiani
Nino
N
Andronikashvili Institute of Physics, 0177 Tbilisi, Georgia.
Abuladze
Marina
M
Kartvelishvili
Tamar
T
Kulikova
Nina
N
Asanishvili
Lali
L
Holman
Hoi-Ying
HY
Sapojnikova
Nelly
N
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
D000975:Antioxidants; D017382:Reactive Oxygen Species; D002857:Chromium; C074702:chromium hexavalent ion; D002374:Catalase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase