LONG-TERM EFFECTS OF PU-239 AND RA-224 ON THE DISTRIBUTION AND PERFORMANCE OF PLURIPOTENT HEMATOPOIETIC PROGENITOR CELLS AND THEIR REGULATORY MICROENVIRONMENT

Experiments are described which investigate the long-term damage to haemopoietic progenitor cells (CFU-S) and their microenvironment in mouse marrow resulting from the administration of leukaemogenic amounts of plutonium-239 and radium-224. Pu-239 (35 Bq g-1 body weight) and Ra-224 (555 Bg g-1 body weight) were injected into 10-12-week-old mice, and numbers, proliferative activity and self-renewal capacity of CFU-S were measured at different locations in femoral marrow at intervals over the following 2 years. Parallel measurements were also made of the quality of the haemopoietic microenvironment by ectopic transplantation of bone marrow cells. There was some recovery from the initial effects of Pu-239 on CFU-S numbers after 3-6 months, although the recovery was not maintained in all marrow fractions. Following Ra-224 administration there was an initial transient increase in CFU-S numbers in the fraction of marrow furthest from bone surfaces but a considerable depression in numbers in other regions of marrow; there was no recovery between 3 and 6 months and subsequent recovery was not complete in all regions of marrow. The differential responses of CFU-S and the haemopoietic microenvironment following Ra-224 or Pu-239 administration seemed in some ways related to the metabolism of the radionuclides. There was a profound reduction in the ability of marrow to generate ossicles when transplanted under the kidney capsule as a result of the administration of either Ra-224 or Pu-239, with only transient recoveries from the effects of Pu-239 at 4 days and at 3 months after injection.