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Effects of Chemotherapeutic Agents on Normal Mouse Bone Marrow Grown in Vitro

Medicine Branch, National Cancer Institute, NIH, Bethesda, Maryland 20014

The effects of several antineoplastic chemotherapeutic drugs on normal mouse bone marrow were studied with the use of an enriched methylcellulose culture system in which marrow forms discrete colonies of myeloid and mononuclear cells. Twenty-four hr after incremental doses, cyclophosphamide, nitrogen mustard, and 1,3-bis(2-chloroethyl)-1-nitrosourea resulted in exponential decreases in the fraction of surviving in vitro colony-forming cells per femur, while vinblastine sulfate, methotrexate, and polyinosinic-polycytidylic acid resulted in dose-response curves which showed that despite increasing doses a maximal kill of colony-forming cells was approached. The repopulation of bone marrow colony-forming cells following a single large dose of cyclophosphamide was also studied. The in vitro culture technique provides another system of assessing bone marrow effects following tumor therapy and may be adaptable to investigation of human bone marrow.

¹ Clinical Associate, Medicine Branch, National Cancer Institute, NIH, Bethesda, Md. 20014.

² Chief, Medicine Branch, National Cancer Institute, NIH, Bethesda, Md. 20014.

Received 4/17/70. Accepted 10/15/70.