Abstract: | 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. |