NDLI: High resistance to cisplatin in human ovarian cancer cell lines is associated with marked increase of glutathione synthesis.

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High resistance to cisplatin in human ovarian cancer cell lines is associated with marked increase of glutathione synthesis.

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High resistance to cisplatin in human ovarian cancer cell lines is associated with marked increase of glutathione synthesis.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Hamilton, T. C. Godwin, A. K. Meister, A. Huang, C. S. O'dwyer, P. J. Anderson, M. E.
Description	Author Affiliation: Godwin AK ( Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111.);
Abstract	Exposure of human ovarian tumor cell lines to cisplatin led to development of cell lines that exhibited increasing degrees of drug resistance, which were closely correlated with increase of the levels of cellular glutathione. Cell lines were obtained that showed 30- to 1000-fold increases in resistance; these cells also had strikingly increased (13- to 50-fold) levels of glutathione as compared with the drug-sensitive cells of origin. These levels of resistance to cisplatin and the cellular glutathione levels are substantially greater than previously reported. Very high cisplatin resistance was associated with enhanced expression of mRNAs for gamma-glutamylcysteine synthetase and gamma-glutamyl transpeptidase; immunoblots showed increase of gamma-glutamylcysteine synthetase but not of glutathione synthetase. Glutathione S-transferase activity was unaffected, as determined with chlorodinitrobenzene as a substrate. These studies suggest the potential value of examining regulation of glutathione synthesis as an indicator of clinical prognosis. The highly resistant cell lines are proving useful for studying the multiple mechanisms by which tumor cells acquire drug- and radiation-resistance.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	7
Volume Number	89
Language	English
Publisher	National Academy of Sciences
Publisher Date	1992-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cisplatin Drug Resistance Glutathione Metabolism Ovarian Neoplasms Physiopathology Gene Expression Glutamate-Cysteine Ligase Glutathione Transferase In Vitro Techniques RNA, Messenger Genetics Tumor Cells, Cultured Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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