Light and electron microscopic investigations on mammalian cells in vitro and in vivo showed that tubulozole-C (R 46 846), the cis-isomer of tubulozole, a new synthetic anticancer drug, interfered with the structure and function of microtubules in both interphase and mitotic cells. The activity of this compound in experimental tumor systems can thus be explained partly by a direct antimitotic effect and partly by the disintegration of the normal subcellular organization of the nondividing cells. At concentrations which affect the microtubule system, tubulozole-C arrested directional migration of transformed cells and malignant invasion in a three-dimensional organ culture system. Investigations in vivo show that malignant L1210 leukemia cells are more susceptible to the antimicrotubular effect of tubulozole-C than are the normal leukocytes of the host. The trans-isomer of tubulozole (tubulozole-T, R 48 265), which has no antitumor activity in vivo, did not affect the microtubule system of cells in vitro or their capacity for directional migration or for malignant invasion.
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