GLUTATHIONE CONTENT IN HUMAN BONE-MARROW AND CIRCADIAN STAGE RELATION TO DNA-SYNTHESIS

DNA synthesis and contents of reduced glutathione (GSH) and oxidized glutathione were determined every 4 hours during a 24-hour period in 70 human bone marrow samples from 10 healthy males. The mean GSH contents during the sampling periods were low, varying from 1.94 to 3.27 nmol/mg protein between the subjects; the mean values for all samples were 2.54 +/- 0.06 nmol/mg protein. The GSH content varied markedly within the individual according to circadian stage (31.0% to 90.2%; mean, 51.4%). Between individuals the mean percentage of cells in DNA synthesis varied from 10.6% to 14.5%, but there was an intraindividual circadian stage-dependent variation, ranging from 48.9% to 274.0% (mean, 126.6%), relative to the lowest value. After adjustment for a slight phase difference between GSH content and DNA synthesis observed for some of the subjects, a statistically significant correlation was found between the GSH content and the fraction of cells in DNA synthesis. The myelosuppressive effect of many chemotherapeutic agents assumed to be detoxified by GSH-dependent mechanism(s) should be considered in the light of the low GSH content in human bone marrow, the circadian variation of DNA synthesis, and the circadian stage-dependent relationship of the GSH content and DNA synthesis.