Long-term effects of plutonium-239 and radium-224 on the distribution and performance of pluripotent haemopoietic progenitor cells and their regulatory microenvironment.

Abstract

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. 239Pu (35 Bq g-1 body weight) and 224Ra (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 239Pu on CFU-S numbers after 3-6 months, although the recovery was not maintained in all marrow fractions. Following 224Ra 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 224Ra or 239Pu 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 224Ra or 239Pu, with only transient recoveries from the effects of 239Pu at 4 days and at 3 months after injection.