Studies on the mechanism of action of cytoxan. Evidence of activation in vivo and in vitro.

Abstract

Summary The reported inactivity of Cytoxan, when assayed directly in mammalian cell cultures, has been confirmed, even with cell lines derived from experimental tumors which respond in vivo to Cytoxan therapy. However, blood serum or crude liver extracts from rats treated with Cytoxan were inhibitory in vitro for serially propagated mammalian cells derived from normal or neoplastic tissue, as well as for cells in primary culture. Experiments in which Cytoxan was incubated in vitro in homogenates of normal and neoplastic mouse tissue indicate that, of the tissues so examined under the present experimental conditions, only the liver homogenates contained a substance (or substances) inhibitory for mammalian cells in culture. The experimental data presented herein support the hypothesis that Cytoxan is a “transport” structure which becomes biologically active only upon appropriate “activation,” and that “activation” sufficient to interfere with cell growth, as adjudged by the present in vitro methods of assay, is accomplished primarily (but probably not exclusively) by the liver.