Effect of L-Asparaginase on the Ability of Normal Mouse Bone Marrow to form Soft Agar Colonies

Abstract

THE enzyme L-asparaginase has anti-tumour activity in man¹. It was initially believed that the drug might act solely on malignant cells which were asparagine-dependent because they lack asparagine synthetase², and considerable attention focused on L-asparaginase as a form of therapy which might, for the first time, exploit a specific nutritional difference between normal and malignant cells³. Extended clinical trials, however, have shown that L-asparaginase may have toxic side effects which reflect an action on normal tissue⁴. Moreover, L-asparaginase has been found to interfere in vitro with the blastogenic response of human lymphocytes to phytohaemagglutinin⁵ and is toxic to normal lymphocytes in culture⁶. I have investigated the effect of L-asparaginase on the ability of normal mouse bone marrow cells to form soft agar colonies. Mouse bone marrow cells which form colonies in agar culture are closely related to those haematopoietic stem cells (colony forming units, CFU) which produce colonies in the spleen⁷.