Journal article
Cellular resistance to oxidative stress is accompanied by resistance to cisplatin: The significance of increased catalase activity and total glutathione in hydrogen peroxide-resistant fibroblasts
Journal of cellular physiology, Vol.156(1), pp.72-79
07/1993
DOI: 10.1002/jcp.1041560111
PMID: 8314861
Abstract
Studies designed to better understand the involvement of cellular resistance to oxidative stress in mechanisms of cellular resistance to cisplatin were undertaken using H2O2-resistant variants of the HA 1 Chinese hamster fibroblast cell line. H2O2-resistant cell lines were resistant to clonogenic inactivation mediated by cisplatin with dose modifying factors at 10% survival of 1.5–3.0, relative to HA 1 cells. The most cisplatin resistant of these cell lines (OC5) also demonstrated fewer DNA–DNA crosslinks induced by cisplatin, relative to HA 1. Since H2O2-resistant cells contained increased catalase activity as well as total glutathione (GSH) content, the involvement of these cellular antioxidants in the resistance to cisplatin toxicity was evaluated. Treatment of HA 1 and H2O2-resistant cell lines (OC5, OC14) with 9 mM aminotriazole reduced catalase activity by 60–65% but had no effect on the cytotoxicity of cisplatin. In contrast, treatment with 5 mM buthionine sulfoximine reduced total GSH by 90% and sensitized the cells to cisplatin cytotoxicity. Furthermore, extracellular reaction of GSH with cisplatin prior to treating HA 1 cells reduced the toxicity of the compound, indicating that this reaction is capable of participating in the detoxification of cisplatin. These results indicate that cellular adaptation to oxidative stress renders cells resistant to DNA damage as well as to cytotoxicity associated with cisplatin treatment. Furthermore, increases in total GSH content (but not catalase activity) appear to partially account for cisplatin resistance demonstrated by H2O2-resistant cell
Details
- Title: Subtitle
- Cellular resistance to oxidative stress is accompanied by resistance to cisplatin: The significance of increased catalase activity and total glutathione in hydrogen peroxide-resistant fibroblasts
- Creators
- Douglas R. Spitz - University of California, San FranciscoJohn W. Phillips - Laboratory of Radiobiology and Environmental Health, University of California, San Francisco, San Francisco, California 94143Donna T. Adams - University of VirginiaC. Michael Sherman - University of VirginiaDennis F. Deen - Brain Tumor Research Center, University of California, San Francisco, San Francisco, California 94143Gloria C. Li - Departments of Medical Physics and Radiation Oncology, Memorial Sloane-Kettering Cancer Center, New York, New York 10021
- Resource Type
- Journal article
- Publication Details
- Journal of cellular physiology, Vol.156(1), pp.72-79
- Publisher
- Wiley Subscription Services, Inc., A Wiley Company
- DOI
- 10.1002/jcp.1041560111
- PMID
- 8314861
- ISSN
- 0021-9541
- eISSN
- 1097-4652
- Number of pages
- 8
- Language
- English
- Date published
- 07/1993
- Academic Unit
- Pathology; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center
- Record Identifier
- 9984313080902771
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