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INVOLVEMENT OF GLUTATHIONE AND GLUTATHIONE‐RELATED ENZYMES IN THE PROTECTION OF NORMAL AND TRISOMIC HUMAN FIBROBLASTS AGAINST DAUNORUBICIN
Author(s) -
Zatorska Agnieszka,
Józwiak Zofia
Publication year - 2002
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1006/cbir.2002.0861
Subject(s) - glutathione , daunorubicin , glutathione reductase , glutathione peroxidase , gpx4 , gpx3 , gpx1 , chemistry , gpx6 , oxidative stress , microbiology and biotechnology , biochemistry , biology , enzyme , leukemia , immunology
We measured the glutathione content, and the activity of glutathione‐related enzymes and DT‐diaphorase in cultured normal (cell line: S‐126) and trisomic (cell lines: S‐158, S‐240) human fibroblasts exposed to daunorubicin (DNR). Determination of reduced and total glutathione levels, and measurement of the activity of glutathione peroxidase, glutathione reductase, glutathione‐S‐transferase and DT‐diaphorase were performed spectrophotometrically. Human fibroblasts were exposed to 4μ m DNR for 2h, and the cells placed in drug‐free medium for 6, 12, 24, 48, and 72h. Cellular levels of GSH and total glutathione decreased following exposure to DNR. However, the ratio of GSH to total glutathione returned to control levels only in trisomic cells. These changes were concomitant with increasing glutathione‐S‐transferase and glutathione reductase activities. DNR also significantly increased the activity of Se‐independent peroxidase and DT‐diaphorase in trisomic fibroblasts. Marked increases in the activity of Se‐dependent peroxidase and DT‐diaphorase alone were seen in normal cells. The results provide the first evidence that DNR can induce alterations in the level of glutathione and glutathione‐dependent enzymes in trisomic fibroblasts as compared to normal cells, which may provide additional protection against daunorubicin‐induced oxidative stress in trisomic fibroblasts.