Enhanced Post-Irradiation Recovery of the Haemopoietic System In Animals Pretreated With A Variety of Cytotoxic Agents

Abstract

Pretreatment of mice with bacterial endotoxin and certain stathmokinetic agents between 1 and 3 days prior to exposure to ionizing radiation reduces radiation lethality. Pretreatment with cytosine arabinoside, methotrexate, nortestosterone and chlorambucil reduced radiation (1000 rad) induced lethality. This reduction could be ascribed to enhanced regeneration of the hemopoietic system in pretreated animals and not to increased survival of colony-forming cells (CFU) in these animals. Regeneration of CFU was underway within 24 h after 900 rad in the pretreated mice but did not start until day 3 in mice treated with .gamma. radiation only. Two agents, i.e., radiation itself (75 or 150 rad) and busulfan (10 mg/kg), did not reduce the lethal effects of subsequent .gamma. irradiation or enhance the regeneration of CFU, even though radiation, like the protective cytosine arabinoside, induces early CFU proliferation. The administration of nucleoside precursors of DNA enhanced regrowth of hemopoietic stem cells to an extent comparable with that of the most effective pretreatment, cytosine arabinoside. Drugs like cytosine arabinoside may operate by causing cell death, providing a source of DNA that can enhance the regrowth of surviving stem cells in the bone marrow.