EFFECT OF IRRADIATION ON THE HEXOSE-MONOPHOSPHATE SHUNT PATHWAY OF HUMAN-LYMPHOCYTES

The radiosensitivity of human peripheral lymphocytes, as indicated by impairment of lymphoblastic transformation in response to phytohemagglutinin, was measured and the effect of hypoxic conditions on the impairment was determined. Lymphoblastic transformation was protected by the anoxic conditions. The effect of X radiation on the total endogenous reduced soluble (nonprotein) sulfhydryl content and on that fraction representing glutathione (GSH) was investigated. The concentration of total reduced sulfhydryl was decreased in both aerobic and anoxic conditions and it was shown that this decrease occurred primarily in the non-GSH fraction. The GSH concentration was maintained by glutathione reductase through its coupling with the hexose monophosphate shunt. The activity of this shunt, which has been shown to protect human cells from damage by highly reactive oxygen species in other systems, was measured by [1-14C]-glucose metabolism and found to increase after aerobic irradiation. However, under anoxic conditions, there was a twofold greater increment than in the aerobically irradiated cells. Evidence from other published studies is cited to support the hypothesis that this represents a competitive reaction of sulfhydryl and oxygen to react with hydrogen deletion radicals formed in macromolecules such as DNA. It is suggested that the oxygen enhancement effect in these cells may result from the destructive reaction of oxygen compounds with such radicals, which is kinetically more favorable than reparative reaction with sulfhydryl.