Determinants of Resistance to Radiation Injury in Blood Granulocytes from Normal Donors and from Patients with Myeloproliferative Disorders

Abstract

Dose-dependent injury to human blood granulocytes was measured within 2 h of X-irradiation, as changes in net 22Na influx and phagocytosing O2 consumption. Among samples from normal donors and patients with chronic myeloproliferative diseases, samples from 10 of 12 patients with chronic granulocytic leukemia exhibited increased sensitivity to injury by radiation. Selected granulocyte constituents which may contribute to inactivation of oxidant and free-radical products of radiation-activated H2O were also measured. These included glutathione and ascorbate contents; superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activities; and capacity to take up and reduce dehydroascorbate. Catalase activity was irregularly higher in radiation-sensitive than in radiation-resistant granulocytes (P = < 0.05). Dehydroascorbate uptake and reduction was consistently low in radiation-sensitive cells (P = < 0.001). Cell capacity to maintain ascorbate in reduced form against oxidant and free-radical stress is probably a part of mechanisms which determine resistance to injury by ionizing radiation in human granulocytes.