Altered mouse bone marrow glutathione and glutathione transferase levels in response to cytotoxins.

The mouse bone marrow has been used as a model for the investigation of the response of cells to cytotoxins and carcinogens. The effects of cyclophosphamide, 1-beta-D-arabinofuranosylcytosine, and X-irradiation on the levels of glutathione and glutathione transferases have been studied. A high dose of cyclophosphamide (500 mg/kg) caused a significant depletion of glutathione levels in marrow, liver, and blood. A lower dose, 75 mg/kg, caused a similar depletion but only in marrow and liver. In this case, 5 to 7 days following treatment, the glutathione content of surviving cells was 1.8- to 3-fold higher than in controls. Glutathione transferase activity was also increased at this time (2- to 3-fold). 1-beta-D-Arabinofuranosylcytosine and X-irradiation also caused a depletion of marrow glutathione and glutathione transferase levels followed increased cellular levels (approximately 2-fold) 3 to 4 days later. Animals given cyclophosphamide (75 mg/kg) survived an otherwise lethal dose of this compound administered 5 to 7 days later. The time course of this effect closely paralleled the higher glutathione and glutathione transferase levels, suggesting a correlation between these effects.