Effect of Irradiation on the Hexose Monophosphate Shunt Pathway of Human Lymphocytes

Abstract

The radiosensitivity of human peripheral lymphocytes, 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-rays on the total endogenous reduced soluble (nonprotein) sulfhydryl content and fraction representing glutathione (GSH) was investigated. The concentration of total reduced sulfhydryl was decreased in aerobic and anoxic conditions. This decrease occurred primarily in the non-GSH fraction. Glutathione reductase maintained the GSH concentration through coupling with the hexose monophosphate shunt. Shunt activity, which protected human cells from damage by highly reactive O2 species in other systems, measured by [1-14C]-glucose metabolism increased after aerobic irradiation. Anoxic conditions created a 2-fold greater increment than aerobically irradiated cells. Other published studies suggest a competitive reaction reaction of sulfhydryl and O2 to react with H deletion radicals formed in macromolecules such as DNA. The O2 enhancement effect in these cells may result from the destructive reaction of O2 compounds with such radicals. This is kinetically more favorable than reparative reaction with sulfhydryl.