An analysis of haemopoietic and microenvironmental populations of mouse bone marrow after treatment with busulphan.

Abstract

The effects of the cytotoxin busulphan (myleran) have been investigated in order to ascertain the unique nature of the lesion which it induces. It is one of only few compounds which can cause marked residual marrow dysfunction and the only drug reported to induce a marrow lesion of such magnitude that after a prolonged interval mice may die of the effects of pancytopaenia resulting from hypoplastic marrow failure. We have found that busulphan has a major microenvironmental effect as assessed by the ability of the marrow to form a complete organ in an ectopic site, which confirms existing evidence from a range of putative stromal assays. The effects upon CFU-S are known to include a selective action against certain subpopulations. Our investigation of the dose relationship of busulphan effects have shown that induction of the prolonged marrow lesion is not dependent on the dose of drug administered, or the fractionation regime employed, and is not dependent therefore on the number of CFU-S removed by the drug. The unique action of busulphan probably rests therefore in its ability to damage the microenvironment and the most primitive stem cells which are closely associated with it, if not entirely dependent on it, for their existence.