This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Arrick, B. A. Articles by Nathan, C. F. Search for Related Content PubMed PubMed Citation Articles by Arrick, B. A. Articles by Nathan, C. F.

Glutathione Metabolism as a Determinant of Therapeutic Efficacy: A Review

Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York 10021

Glutathione, as the chief nonprotein intracellular sulfhydryl, affects the efficacy and interactions of a variety of antineoplastic interventions, mainly through nucleophilic thioether formation or oxidation-reduction reactions. Thus, glutathione plays a role in the detoxification and repair of cellular injury by such diverse agents as mechlorethamine, melphalan, cyclophosphamide, nitrosoureas, 6-thiopurine, 4'-(9-acridinylamino)methanesulfon-m-anisidide, the quinone antibiotics (including Adriamycin, daunorubicin, and mitomycin C), the sesquiterpene lactones (such as vemolepin), and other sulfhydryl-reactive diterpenes (like jatrophone). Glutathione may play a similar role in host and tumor cell responses to radiation, hyperthermia, and the reactive reduction products of oxygen secreted by inflammatory cells. Further, glutathione participates in the formation of toxic metabolites of such chemotherapeutics as azathioprine and bleomycin and may affect the cellular uptake of other agents, such as methotrexate. It seems likely that alterations in glutathione metabolism of tumor or host as a result of one therapeutic intervention may affect the outcome of concurrent treatments. Knowledge of these interactions may be useful in designing combination therapy for neoplastic disease.

Received 3/ 2/84. Accepted 7/13/84.

This article has been cited by other articles:

				J. Prousky The Treatment of Pulmonary Diseases and Respiratory-Related Conditions with Inhaled (Nebulized or Aerosolized) Glutathione Evid. Based Complement. Altern. Med., March 1, 2008; 5(1): 27 - 35. [Abstract] [Full Text] [PDF]

				I. Inci, W. Zhai, S. Arni, S. Hillinger, P. Vogt, and W. Weder N-Acetylcysteine Attenuates Lung Ischemia-Reperfusion Injury After Lung Transplantation Ann. Thorac. Surg., July 1, 2007; 84(1): 240 - 246. [Abstract] [Full Text] [PDF]

				M. T. Forrester, M. W. Foster, and J. S. Stamler Assessment and Application of the Biotin Switch Technique for Examining Protein S-Nitrosylation under Conditions of Pharmacologically Induced Oxidative Stress J. Biol. Chem., May 11, 2007; 282(19): 13977 - 13983. [Abstract] [Full Text] [PDF]

				M. T. M. RAIJMAKERS, P. L. M. ZUSTERZEEL, E. A. P. STEEGERS, M. P. C. HECTORS, P. N. M. DEMACKER, and W. H. M. PETERS Plasma Thiol Status in Preeclampsia Obstet. Gynecol., February 1, 2000; 95(2): 180 - 184. [Abstract] [Full Text] [PDF]

				P. Poli, A. Buschini, A. Candi, and C. Rossi Bleomycin genotoxicity alteration by glutathione and cytochrome P-450 cellular content in respiratory proficient and deficient strains of Saccharomyces cerevisiae Mutagenesis, March 1, 1999; 14(2): 233 - 238. [Abstract] [Full Text] [PDF]

				M. Summerhayes Review : Amifostine and other chemoprotective agents in cancer chemotherapy: A brief review Journal of Oncology Pharmacy Practice, December 1, 1995; 1(4): 21 - 31. [Abstract] [PDF]

				A. Yokomizo, K. Kohno, M. Wada, M. Ono, C. S. Morrow, K. H. Cowan, and M. Kuwano Markedly Decreased Expression of Glutathione S-Transferase [IMAGE] Gene in Human Cancer Cell Lines Resistant to Buthionine Sulfoximine, an Inhibitor of Cellular Glutathione Synthesis J. Biol. Chem., August 18, 1995; 270(33): 19451 - 19457. [Abstract] [Full Text] [PDF]

				J. Carretero, E. Obrador, J. M. Esteve, A. Ortega, J. A. Pellicer, F. V. Sempere, and J. M. Estrela Tumoricidal Activity of Endothelial Cells. INHIBITION OF ENDOTHELIAL NITRIC OXIDE PRODUCTION ABROGATES TUMOR CYTOTOXICITY INDUCED BY HEPATIC SINUSOIDAL ENDOTHELIUM IN RESPONSE TO B16 MELANOMA ADHESION IN VITRO J. Biol. Chem., July 6, 2001; 276(28): 25775 - 25782. [Abstract] [Full Text] [PDF]