Carmichael J, Adams D J, Ansell J, Wolf C R
Cancer Res. 1986 Feb;46(2):735-9.
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.
在初次耗竭后,给予低剂量环磷酰胺后,小鼠骨髓中的谷胱甘肽和谷胱甘肽转移酶水平会短暂升高。后续给药时也观察到类似效果。通过荧光激活细胞分选仪对各种骨髓细胞群进行分离显示,谷胱甘肽和谷胱甘肽转移酶水平的升高仅限于粒细胞部分。这很可能为低“预激”剂量环磷酰胺对后续致死剂量的保护作用提供了解释。粒细胞谷胱甘肽和谷胱甘肽转移酶水平的变化也可以在外周循环中监测到。细胞毒性损伤导致细胞内谷胱甘肽水平升高似乎是细胞对细胞毒素的一种普遍反应,在抗肿瘤治疗以及化学毒性和致癌性的引发中可能都很重要。