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Glutathione and Glutathione Transferase Levels in Mouse Granulocytes following Cyclophosphamide Administration¹

Imperial Cancer Research Fund, Laboratory of Molecular Pharmacology and Drug Metabolism, Department of Biochemistry, George Square [J. C., D. J. A., C. R. W.], and Department of Zoology, The King's Buildings [J. A.], University of Edinburgh, Edinburgh, United Kingdom

Following an initial depletion, glutathione and glutathione transferase levels are transiently increased in mouse bone marrow following the administration of a low dose of cyclophosphamide. Similar effects are observed on subsequent administration of the drug. The separation of various bone marrow populations on a fluorescence-activated cell sorter has shown that increase in glutathione and glutathione transferase levels are restricted to the granulocytic fraction. This may well provide an explanation for the protective effect of a low ‘priming’ dose of cyclophosphamide against a subsequent lethal dose. The changes in granulocytic glutathione and glutathione transferase levels can also be monitored in the peripheral circulation. The enhanced levels of glutathione in cells resulting from cytotoxic insult appear to be a general response of cells to cytotoxins and may be important in both antitumor therapy as well as the initiation of chemical toxicity and carcinogenicity.

¹ The financial support of the Cancer Research Campaign, Grant No. SP 1610, is gratefully acknowledged.

² Present address: National Cancer Institute, Naval Medical Oncology Branch, Bethesda, MD.

³ Present address: Department of Microbiology, University of Leeds, Leeds, LS2 9JT, United Kingdom.

⁴ To whom requests for reprints should be addressed.

Received 5/29/85. Revised 10/23/85. Accepted 10/24/85.

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